Cancer

Definition

Cancer is not just one disease, but a large group of almost 100 diseases. Its two main characteristics are uncontrolled growth of the cells in the human body and the ability of these cells to migrate from the original site and spread to distant sites. If the spread is not controlled, cancer can result in death.

Description

One out of every four deaths in the United States is from cancer. It is second only to heart disease as a cause of death in the states. About 1.2 million Americans are diagnosed with cancer annually; more than 500,000 die of cancer annually.

Cancer can attack anyone. Since the occurrence of cancer increases as individuals age, most of the cases are seen in adults, middle-aged or older. Sixty percent of all cancers are diagnosed in people who are older than 65 years of age. The most common cancers are skin cancer, lung cancer, colon cancer, breast cancer (in women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph node cancer (leukemias and lymphomas) are also included among the 12 major cancers that affect most Americans.

Cancer, by definition, is a disease of the genes. A gene is a small part of DNA, which is the master molecule of the cell. Genes make "proteins," which are the ultimate workhorses of the cells. It is these proteins that allow our bodies to carry out all the many processes that permit us to breathe, think, move, etc.

Throughout people's lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt the genes and produce faulty proteins. This causes the cell to become abnormal and lose its restraints on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a "tumor" or neoplasm (medical term for cancer meaning "new growth").

In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some mutant cells may escape immune detection and survive to become tumors or cancers.

Tumors are of two types, benign or malignant. A benign tumor is not considered cancer. It is slow growing, does not spread or invade surrounding tissue, and once it is removed, doesn't usually recur. A malignant tumor, on the other hand, is cancer. It invades surrounding tissue and spreads to other parts of the body. If the cancer cells have spread to the surrounding tissues, even after the malignant tumor is removed, it generally recurs.

A majority of cancers are caused by changes in the cell's DNA because of damage due to the environment. Environmental factors that are responsible for causing the initial mutation in the DNA are called carcinogens, and there are many types.

There are some cancers that have a genetic basis. In other words, an individual could inherit faulty DNA from his parents, which could predispose him to getting cancer. While there is scientific evidence that both factors (environmental and genetic) play a role, less than 10% of all cancers are purely hereditary. Cancers that are known to have a hereditary link are breast cancer, colon cancer, ovarian cancer, and uterine cancer. Besides genes, certain physiological traits could be inherited and could contribute to cancers. For example, inheriting fair skin makes a person more likely to develop skin cancer, but only if he or she also has prolonged exposure to intensive sunlight.

There are several different types of cancers:

• Carcinomas are cancers that arise in the epithelium (the layer of cells covering the body's surface and lining the internal organs and various glands). Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two types: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.
• Melanomas also originate in the skin, usually in the pigment cells (melanocytes).
• Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle and blood vessels.
• Cancers of the blood and lymph glands are called leukemias and lymphomas respectively.
• Gliomas are cancers of the nerve tissue.

Causes and symptoms

The major risk factors for cancer are: tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment and pollution.

JANETD. ROWLEY (1925–)

Janet Davison Rowley was born in New York City on April 5, 1925, to Ethel Mary (Ballantyne) and Hurford Henry Davison. Rowley attended the University of Chicago, earning her B.S. degree in 1946 and her M.D. degree in 1948. She also married Donald A. Rowley in 1948, and the couple ultimately had four sons. Rowley completed both her internship and residency at Chicago hospitals before returning to the University of Chicago Medical School where she conducted research from 1962–1969. She became an associate professor, and finally, in 1977, earned her position as a full professor.

Rowley's research has focused on understanding cancer, with special emphasis on its cytogenetic causes. Her development and use of Giemsa and quinacrine stains enabled Rowley to discover oncogenes and to ultimately show a consistent shifting or translocation of genetic material in chronic myeloid leukemia cells. Rowley's discoveries and continued research have shown that malignant cells in humans undergo this translocation and deletion of genes that cause tumors to grow. Her research has given oncologists new pathways to explore concerning gene therapies for the treatment of cancer.

Co-editor and co-founder of the journal, Genes, Chromosomes and Cancer, Rowley has published an abundance of materials including Chromosome Changes in Leukemia (1978), Genes and Cancer (1984), and Advances in Understanding Genetic Changes in Cancer (1992). Rowley has also received many awards and honors for her work and research.

According to estimates of the American Cancer Society (ACS), approximately 40% of cancer deaths in 1998 were due to tobacco and excessive alcohol use. An additional one-third of the deaths were related to diet and nutrition. Many of the one million skin cancers diagnosed in 1998 were due to over-exposure to ultraviolet light from the sun's rays.

Tobacco

Eighty to 90% of lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, breast, and kidney as well. Recently, scientists have also shown that second-hand smoke (or passive smoking) can increase one's risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers, such as liver cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers.

Diet

Thirty-five percent of all cancers are due to dietary causes. Excessive intake of fat leading to obesity has been associated with cancers of the breast, colon, rectum, pancreas, prostate, gall bladder, ovaries, and uterus.

Sexual and reproductive behavior

The human papillomavirus, which is sexually transmitted, has been shown to cause cancer of the cervix. Having too many sex partners and becoming sexually active early has been shown to increase one's chances of contracting this disease. In addition, it has also been shown that women who don't have children or have children late in life have an increased risk for both ovarian and breast cancer.

Infectious agents

In the last 20 years, scientists have obtained evidence to show that approximately 15% of the world's cancer deaths can be traced to viruses, bacteria, or parasites. The most common cancer-causing pathogens and the cancers associated with them are shown in table form.

Family history

Certain cancers like breast, colon, ovarian, and uterine cancer recur generation after generation in some families. A few cancers, such as the eye cancer "retinoblastoma," a type of colon cancer, and a type of breast cancer known as "early-onset breast cancer," have been shown to be linked to certain genes that can be tracked within a family. It is therefore possible that inheriting particular genes makes a person susceptible to certain cancers.

Occupational hazards

There is evidence to prove that certain occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber and gas workers; skin and lung cancer with smelters, gold miners and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone and bone marrow cancer with radiologists and uranium miners.

Environment

Radiation is believed to cause 1-2% of all cancer deaths. Ultra-violet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x rays, radon gas, and ionizing radiation from nuclear material.

Pollution

Several studies have shown that there is a well-established link between asbestos and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollution occurs when dangerous chemicals from the industries escape into the surrounding environment. It has been estimated that 1% of cancer deaths are due to air, land, and water pollution.

Cancer is a progressive disease, and goes through several stages. Each stage may produce a number of symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs, and blood vessels. This causes pain and some pressure which may be the earliest warning signs of cancer.

Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color, or shape of a wart or a mole
• a sore that does not heal
• persistent cough, hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty in swallowing
• any change in bowel or bladder habits

Many other diseases, besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked, as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers such as breast cancer may not have any early symptoms. Therefore, it is important to undergo routine screening tests such as breast self-exams and mammograms.

Diagnosis

Diagnosis begins with a thorough physical examination and a complete medical history. The doctor will observe, feel and palpate (apply pressure by touch) different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue.

As part of the physical exam, the doctor will inspect the oral cavity, or the mouth. By focusing a light into the mouth, he will look for abnormalities in color, moisture, surface texture, or presence of any thickening or sore in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat. To detect thyroid cancer, the doctor will observe the front of the neck for swelling. He may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland (located at the base of the neck) to detect any nodules or tenderness. As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms and in the groin. Many illnesses and cancers cause a swelling of the lymph nodes.

The doctor may conduct a thorough examination of the skin to look for sores that have been present for more than three weeks and that bleed, ooze, or crust; irritated patches that may itch or hurt, and any change in the size of a wart or a mole.

Examination of the female pelvis is used to detect cancers of the ovaries, uterus, cervix, and vagina. In the visual examination, the doctor looks for abnormal discharges or the presence of sores. Then, using gloved hands the physician palpates the internal pelvic organs such as the uterus and ovaries to detect any abnormal masses. Breast examination includes visual observation where the doctor looks for any discharge, unevenness, discoloration, or scaling. The doctor palpates both breasts to feel for masses or lumps.

For males, inspection of the rectum and the prostate is also included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for any growths, tumors, or other abnormalities. The doctor also conducts an examination of the testes, where the doctor observes the genital area and looks for swelling or other abnormalities. The testicles are palpated to identify any lumps, thickening or differences in the size, weight and firmness.

If the doctor detects an abnormality on physical examination, or the patient has some symptom that could be indicative of cancer, the doctor may order diagnostic tests.

Laboratory studies of sputum (sputum cytology), blood, urine, and stool can detect abnormalities that may indicate cancer. Sputum cytology is a test where the phlegm that is coughed up from the lungs is microscopically examined. It is often used to detect lung cancer. A blood test for cancer is easy to perform, usually inexpensive and risk-free. The blood sample is obtained by a lab technician or a doctor by inserting a needle into a vein and is relatively painless. Blood tests can be either specific or non-specific. Often, in certain cancers, the cancer cells release particular proteins (called tumor markers ) and blood tests can be used to detect the presence of these tumor markers. However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several non-cancerous conditions also produce positive results. Blood tests are generally more useful in monitoring the effectiveness of the treatment, or in following the course of the disease and detecting recurrent disease.

Imaging tests such as computed tomography scans (CT scans), magnetic resonance imaging (MRI), ultrasound and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless and easily accessible. In order to increase the information obtained from a conventional x ray, air or a dye (such as barium or iodine) may be used as a contrast medium to outline or highlight parts of the body.

The most definitive diagnostic test is the biopsy, wherein a piece of tissue is surgically removed for microscope examination. Besides confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer and the extent of its spread. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests.

Screening examinations conducted regularly by healthcare professionals can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testis, tongue, mouth, and skin at early stages, when treatment is more likely to be successful. Some of the routine screening tests recommended by the ACS are sigmoidoscopy (for colorectal cancer), mammography (for breast cancer), pap smear (for cervical cancer ), and the PSA test (for prostate cancer). Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting the tumors before the symptoms become serious.

A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one's risk of getting cancers. These new techniques include genetic testing, where molecular probes are used to identify mutations in certain genes that have been linked to particular cancers. At present, however, there are a lot of limitations to genetic testing and its utility appears ambiguous, emphasizing the need to develop better strategies for early detection.

Treatment

Treatment and prevention of cancers continue to be the focus of a great deal of research. In 2003, research into new cancer therapies included cancertargeting gene therapy, virus therapy, and a drug that stimulated apoptosis, or self-destruction of cancer cells, but not healthy cells. However, all of these new therapies take years of clinical testing and research.

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms, and it is always tailored to the individual patient. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient's age, sex, general health status and personal treatment preferences. The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation.

Surgery

Surgery is the removal of a visible tumor and is the most frequently used cancer treatment. It is most effective when a cancer is small and confined to one area of the body.

Surgery can be used for many purposes.

• Treatment. Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some part of the normal surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes may be examined and sometimes are removed as well.
• Preventive surgery. Preventive or prophylactic surgery involves removal of an abnormal looking area that is likely to become malignant over time. For example, 40% of people with a colon disease known as ulcerative colitis, ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed and reduce the risk significantly.
• Diagnostic purposes. The most definitive tool for diagnosing cancer is a biopsy. Sometimes, a biopsy can be performed by inserting a needle through the skin. However, at other times, the only way to obtain a tissue sample for biopsy is by performing a surgical operation.
• Cytoreductive surgery is a procedure where the doctor removes as much of the cancer as possible, and then treats the remaining area with radiation therapy or chemotherapy or both.
• Palliative surgery is aimed at curing the symptoms, not the cancer. Usually, in such cases, the tumor is so large or has spread so much that removing the entire tumor is not an option. For example, a tumor in the abdomen may be so large that it may press on and block a portion of the intestine, interfering with digestion and causing pain and vomiting. "Debulking surgery" may remove a part of the blockage and relieve the symptoms. In tumors that are dependent on hormones, removal of the organs that secrete the hormones is an option. For example, in prostate cancer, the release of testosterone by the testicles stimulates the growth of cancerous cells. Hence, a man may undergo an "orchiectomy" (removal of testicles) to slow the progress of the disease. Similarly, in a type of aggressive breast cancer, removal of the ovaries (oophorectomy ) will stop the synthesis of hormones from the ovaries and slow the progression of the cancer.

Radiation therapy

Radiation kills tumor cells. Radiation is used alone in cases where a tumor is unsuitable for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. In the external form, the radiation is aimed at the tumor from outside the body. In internal radiation (also known as brachytherapy), a radioactive substance in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection or insertion in a sealed container.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. It destroys the hard-to-detect cancer cells that have spread and are circulating in the body. Chemotherapeutic drugs can be taken either orally (by mouth) or intravenously, and may be given alone or in conjunction with surgery, radiation or both.

When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or "neoadjuvant chemotherapy." An advantage of neoadjuvant chemotherapy is that since the cancer cells have not been exposed to anti-cancer drugs, they are especially vulnerable. It can therefore be used effectively to reduce the size of the tumor for surgery or target it for radiation. However, the toxic effects of neoadjuvant chemotherapy are severe. In addition, it may make the body less tolerant to the side effects of other treatments that follow such as radiation therapy. The more common use of chemotherapy is adjuvant therapy, which is given to enhance the effectiveness of other treatments. For example, after surgery, adjuvant chemotherapy is given to destroy any cancerous cells that still remain in the body. In 2003, a new technique was developed to streamline identification of drug compounds that are toxic to cancerous cells but not to healthy cells. The technique identified nine dugs, one of which had never before been identified for use in cancer treatment. Researchers began looking into developing the new drug for possible use.

Immunotherapy

Immunotherapy uses the body's own immune system to destroy cancer cells. This form of treatment is being intensively studied in clinical trials and is not yet widely available to most cancer patients. The various immunological agents being tested include substances produced by the body (such as the interferons, interleukins, and growth factors), monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer. Instead, they are designed to treat people who already have the disease. Cancer vaccines work by boosting the body's immune system and training the immune cells to specifically destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for some types of cancers that are hormone-dependent and grow faster in the presence of particular hormones. These include cancer of the prostate, breast, and uterus. Hormone therapy involves blocking the production or action of these hormones. As a result the growth of the tumor slows down and survival may be extended for several months or years.

Bone marrow transplantation

The bone marrow is the tissue within the bone cavities that contains blood-forming cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also destroys bone marrow. Replacing the bone marrow with healthy cells counteracts this adverse effect. A bone marrow transplant is the removal of marrow from one person and the transplant of the blood-forming cells either to the same person or to someone else. Bone-marrow transplantation, while not a therapy in itself, is often used to "rescue" patients, by allowing those with cancer to undergo aggressive therapy.

Many different specialists generally work together as a team to treat cancer patients. An oncologist is a physician who specializes in cancer care. The oncologist provides chemotherapy, hormone therapy, and any other non-surgical treatment that does not involve radiation. The oncologist often serves as the primary physician and coordinates the patient's treatment plan.

The radiation oncologist specializes in using radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians involved with treating women's and children's cancers respectively. Many other specialists also may be involved in the care of a cancer patient. For example, radiologists specialize in the use of x rays, ultrasounds, CT scans, MRI imaging and other techniques that are used to diagnose cancer. Hematologists specialize in disorders of the blood and are consulted in case of blood cancers and bone marrow cancers. The samples that are removed for biopsy are sent to a laboratory, where a pathologist examines them to determine the type of cancer and extent of the disease. Only some of the specialists who are involved with cancer care have been mentioned above. There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient should it become necessary.

Alternative treatment

There are a multitude of alternative treatments available to help the person with cancer. They can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. Alternative treatment of cancer is a complicated arena and a trained health practitioner should be consulted.

Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain has not been clinically proven, many cancer patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine also have been shown to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Certain foods including many vegetables, fruits, and grains are believed to offer protection against various cancers. However, isolation of the individual constituent of vegetables and fruits that are anti-cancer agents has proven difficult. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots have been shown to protect against cancer. Studies have shown that eating a diet rich in fiber as found in fruits and vegetables reduces the risk of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast, and colon cancer.

Certain drugs, which are currently being used for treatment, could also be suitable for prevention. For example, the drug tamoxifen (Nolvadex), which has been very effective against breast cancer, is currently being tested by the National Cancer Institute for its ability to prevent cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium. More trials are needed to explain these intriguing connections.

Prognosis

"Lifetime risk" is the term that cancer researchers use to refer to the probability that an individual over the course of a lifetime will develop cancer or die from it. In the United States, men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African Americans are more likely to develop cancer than whites. African Americans are also 30% more likely to die of cancer than whites.

Most cancers are curable if detected and treated at their early stages. A cancer patient's prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer. In addition, the patient's age, general health status and the effectiveness of the treatment being pursued also are important factors.

To help predict the future course and outcome of the disease and the likelihood of recovery from the disease, doctors often use statistics. The five-year survival rates are the most common measures used. The number refers to the proportion of people with cancer who are expected to be alive, five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, it cannot be used to indicate individual prognosis, because no two patients are exactly alike.

Prevention

According to nutritionists and epidemiologists from leading universities in the United States, a person can reduce the chances of getting cancer by following some simple guidelines:

• eating plenty of vegetables and fruits
• exercising vigorously for at least 20 minutes every day
• avoiding excessive weight gain
• avoiding tobacco (even second hand smoke)
• decreasing or avoiding consumption of animal fats and red meats
• avoiding excessive amounts of alcohol
• avoiding the midday sun (between 11 A.M. and 3 P.M.) when the sun's rays are the strongest
• avoiding risky sexual practices
• avoiding known carcinogens in the environment or work place

KEY TERMS

Benign— Mild, nonmalignant. Recovery is favorable with treatment.

Biopsy— The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Bone marrow— Spongy material that fills the inner cavities of the bones. The progenitors of all the blood cells are produced in this bone marrow.

Carcinogen— Any substance capable of causing cancer by mutating the cell's DNA.

Chemotherapy— Treatment with certain anticancer drugs.

Epithelium— The layer of cells covering the body's surface and lining the internal organs and various glands.

Hormone therapy— Treatment of cancer by inhibiting the production of hormones such as testosterone and estrogen.

Immunotherapy— Treatment of cancer by stimulating the body's immune defense system.

Malignant— A general term for cells and the tumors they form that can invade and destroy other tissues and organs.

Metastasis— The spread of cancer from one part of the body to another.

Radiation therapy— Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Sore— An open wound, bruise or lesion on the skin.

Tumor— An abnormal growth resulting from a cell that lost its normal growth control restraints and started multiplying uncontrollably.

X rays— High-energy radiation used in high doses, either to diagnose or treat disease.

In addition, following the advice of physicians in refraining from certain activities or drugs that are proven as risk factors for certain cancers can help lower one's risk. For instance, while physicians have long known a small increased risk for breast cancer was linked to use of HRT, a landmark study released in 2003 proved the risk was greater than thought. The Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more her risk increased.

Resources

BOOKS

Simone, Joseph V. "Oncology: Introduction." In Cecil Textbook of Medicine, edited by Russel L. Cecil, et al. Philadelphia: W.B. Saunders Company, 2000.

PERIODICALS

"HRT Linked to Higher Breast Cancer Risk, Later Diagnosis, Abnormal Mammograms." Women's Health Weekly July 17, 2003: 2.

"New Way to Stop Cancer Cell Growth Described." Gene Therapy Weekly December 12, 2002: 9.

"Researchers Find New Way to Trigger Self-Destruction of Certain Cancer Cells." Biotech Week July 16, 2003: 285.

"Technique Streamlines Search for Anticancer Drugs." Cancer Weekly April 15, 2003: 62.

"Virus Therapy Attacks Cancer Cells." Cancer Weekly July 29, 2003: 50.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E. Atlanta, GA 30329 (800) 227-2345. 〈http://www.cancer.org〉.

Cancer Research Institute (National Headquarters). 681, Fifth Avenue, New York, NY 10022 (800) 992-2623. 〈http://www.cancerresearch.org〉.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, Maryland, 20892 (800) 422-6237. 〈http://wwwicic.nci.nih.gov〉.

Cancer

Definition

Cancer is a group of diseases characterized by uncontrolled growth of tissue cells in the body and the invasion by these cells into nearby tissue and migration to distant sites.

Description

Cancer results from alterations (mutations) in genes that make up DNA, the master molecule of the cell. Genes make proteins, which are the ultimate workhorses of the cells, responsible for the many processes that permit humans to breathe, think, and move, among other functions. Some of these proteins control the orderly growth, division, and reproduction of normal tissue cells. Gene mutations can produce faulty proteins, which in turn produce abnormal cells that no longer divide and reproduce in an orderly manner. These abnormal cells divide uncontrollably and eventually form a new growth known as a tumor or neoplasm. A healthy immune system can usually recognize neoplastic cells and destroy them before they divide. However, mutant cells may escape immune detection and become tumors or cancers.

Studies of the origins of cancer have shown that a combination of genetic influences and environmental causes over time triggers gene mutations, which may explain why most cancers are seen in adults of middle age or older (60%) and cancer is rare children. Many cancers have been shown to result from exposure to environmental toxins (carcinogens) and related alterations in DNA. Faulty DNA can also be inherited, predisposing an individual to develop cancer, although fewer than 10 percent of cancers are purely hereditary. Hereditary links have been shown in cancers of the breast, colon, ovaries, and uterus. Inherited physiological traits can also contribute to cancer, such as inheriting fair skin increasing the risk of skin cancer, but only if accompanied by prolonged exposure to intensive sunlight.

Tumors can be benign or malignant. A benign tumor is not cancer. It is slow growing, does not invade surrounding tissue, and once removed, does not usually recur. A malignant tumor is cancerous. It invades surrounding tissue and spreads to nearby or distant organs (metastasis). If the cancer cells have spread to surrounding tissue, even after the malignant tumor is removed, it will typically recur.

Cancer falls into several general categories:

• Carcinoma (90% of all cancer) are solid tumors arising in the layer of cells (epithelium) covering the body's surface and lining internal organs and glands. Adenocarcinomas develop in an organ or gland and squamous cell carcinomas originate in the skin.
• Melanoma originates in the skin, usually in pigment cells (melanocytes).
• Sarcoma is cancer of supporting tissue such as bone, muscle, and blood vessels.
• Leukemias and lymphomas are cancers of the blood and lymph glands.
• Gliomas are cancers of the nerve tissue.

The most common cancers affecting adults are cancer of the skin, lung, colon, breast, and prostate. Cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and the leukemias and lymphomas are among the 12 major cancers affecting Americans of all ages. Although children and adolescents do develop solid tumors, the most common high-risk cancers among children are:

• acute myeloid leukemia
• acute lymphoblastic leukemia
• neuroblastoma
• glioma
• sarcoma of bone (osteosarcoma) and soft tissue

Demographics

Childhood cancer is rare, occurring in about 14 in 100,000 children in the United States each year. However, in the entire U.S. population, one of every four deaths is from cancer, second only to deaths from heart disease. About 1.2 million cancer cases are diagnosed annually and more than 500,000 die, of whom 2,700 are children or adolescents.

Causes and symptoms

Genetic predisposition, environmental causes, and individual developmental problems are responsible for most childhood cancer. The presence of other disorders, such as Down syndrome , has also been shown to be associated with cancer in children. The major risk factors that apply to adult cancer are tobacco, alcohol, sexual and reproductive behavior, and occupation, none of which increases risk in children. Other well-known risk factors, such as family history, infectious agents, diet, environmental toxins, and pollution, can apply equally to children.

Tobacco

Approximately 80 to 90 percent of lung cancer cases occur in smokers. Smoking is also the leading cause of bladder cancer and has been shown to contribute to cancers of the upper respiratory tract, esophagus, larynx, kidney, pancreas, stomach, and possibly breast as well. Second-hand smoke (passive smoking) has been shown to increase cancer risk in children and adults who live with smokers.

Infectious agents

Cancer deaths worldwide can be traced to viruses, bacteria, or parasites. Epstein-Barr virus (EBV), for example, is associated with lymphoma, the hepatitis viruses are associated with liver cancer, HIV is associated with Kaposi's sarcoma, and the bacteria Helicobacter pylori is associated with stomach cancer.

Genetic predisposition

Certain cancers such as breast, colon, ovarian, and uterine cancer recur generation after generation in some families. Eye cancer (retinoblastoma ), a type of colon cancer, and early-onset breast cancer have been shown to be linked to the inheritance of specific genes.

Environmental sources

Radiation is believed to cause 1 to 2 percent of all cancer deaths. Ultraviolet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x-rays, radon gas, and ionizing radiation from nuclear material.

Pollution

Studies have established links between environmental toxins, such as asbestos, and cancer. Chlorination of water may account for a small rise in cancer risk. However, the main danger from pollutants occurs when toxic industrial chemicals are released into the surrounding environment. As of 2004 an estimated 1 percent of cancer deaths are believed to be due to air, land, and water pollution.

Cancer is a progressive disease that goes through several stages, each producing a number of symptoms. Early symptoms can be produced by the growth of a solid tumor in an organ or gland. A growing tumor may press on nearby nerves, organs, and blood vessels, causing pain and pressure that may be the first warning signs of cancer. Other symptoms can include sores that do not heal, growths on the skin or below the skin, unusual bleeding, difficulty digesting food or swallowing, and changes in bowel or bladder function. Fever can be present as well as fatigue and weakness.

When to call the doctor

Despite the fact that there are hundreds of different types of cancer, each producing different symptoms, the American Cancer Society has established the following seven symptoms as possible warning signals of cancer:

• changes in the size, color, or shape of a wart or a mole
• a sore that does not heal
• persistent cough , hoarseness, or sore throat
• a lump or thickening in the breast or elsewhere
• unusual bleeding or discharge
• chronic indigestion or difficulty swallowing
• any change in bowel or bladder habits

Parents should report any such symptoms to the pediatrician along with unexplained fever or frequent infections. Vision problems, weight loss, lack of appetite, depression, swollen glands, paleness, or general weakness are other reasons for parents to consult the pediatrician. Generally, the earlier cancer is diagnosed and treated, the better the chance of a cure, although not all cancers have early symptoms.

Diagnosis

Diagnosis begins with a complete medical history, including family history of cancer, and a thorough physical examination. The doctor observes and palpates (applies pressure by touch) different parts of the body in order to identify any variations from normal size, feel, and texture of an organ or tissue. The doctor looks inside the mouth for abnormalities in color, moisture, surface texture, or the presence of any thickening or sores in the lips, tongue, gums, the roof of the mouth, or the throat. The doctor observes the front of the neck for swelling and may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland at the base of the neck, looking for nodules or tenderness. The doctor also palpates the lymph nodes in the neck, under the arms, and in the groin, looking for enlargement. The skin is examined for sores that are slow to heal, especially those that bleed, ooze, or crust; irritated patches that may itch or hurt; and any change in the size of a wart or a mole.

In adolescent females, a pelvic exam may be conducted to detect cancers of the ovaries, uterus, cervix, and vagina. The doctor first looks for abnormal discharges or the presence of sores. Then the internal pelvic organs such as the uterus and ovaries are palpated (touched while applying gentle pressure) to detect abnormal masses. Breast examination evaluates unevenness, discoloration, or scaling; both breasts are palpated to feel for masses or lumps.

In adolescent males, inspection of the rectum and prostate may be included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for growths, tumors, or other abnormalities. The testes are examined visually, looking for unevenness, swelling, or other abnormalities. The testicles are palpated to identify lumps, thickening or differences in size, weight, or firmness.

If an abnormality is detected on physical examination, or symptoms suggestive of cancer are noted, diagnostic tests will be performed. Laboratory studies of sputum, blood, urine, and stool can detect abnormalities that may confirm cancer. Sputum cytology involves the microscopic examination of phlegm that is coughed up from the lungs. Tumor markers, specific proteins released by certain types of cancer cells, can be detected by performing a test on venous blood. If leukemia or lymphoma is suspected, a complete blood count (CBC) with peripheral smear (differential) is done to evaluate the number, appearance, and maturity of red blood cells (RBCs) and white blood cells (WBCs) and to measure hemoglobin, hematocrit, and platelet count . A bone marrow biopsy may be done to determine what type of cells is present in the bone marrow. Blood chemistries will be done to help determine if liver or kidney problems are present. Blood chemistries are also useful in monitoring the effectiveness of treatment for all types of cancer and in following the course of the disease and detecting recurrences.

Diagnostic imaging techniques such as computed tomography (CT scans), magnetic resonance imaging (MRI), ultrasound, and fiberoptic scope examinations (such as colonoscopy or sigmoidoscopy) can help determine the location, size, and characteristics of a tumor even if it is deep within the body. Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless, and easily accessible. In order to increase the information obtained from a conventional x ray, air or contrast media (such as barium or iodine) may be used to enhance the images.

The most definitive diagnostic test for cancer is a biopsy, which is the surgical removal of a piece of suspect tissue for staining and microscope examination (cytochemistry). By examining certain cell characteristics, abnormalities can be identified and the presence of specific types of cells can be diagnostic for certain cancers. The biopsy provides information about the type of cancer, its stage, the aggressiveness of the cancer in invading nearby tissue or organs, and the extent of metastases at diagnosis. The pathologist who evaluates cancer cells in biopsied tissue designates the cancer as being stage I, II, III, or IV, in terms of the degree of metastasis.

Newer molecular and cellular diagnostic testing, such as polymerase chain reaction (PCR), allows the molecular genetic analysis of tumors. Cytogenetic analysis of tumor chromosomes, for example, can identify structural abnormalities that may explain the unique origins of cancer in an individual child. Spectral karyotyping (SKY), an advanced method of screening chromosomes for numeric and structural abnormalities, is used to evaluate pediatric tumors. Gene sequences can also be evaluated in a method (comparative genomic hybridization) that compares samples from a tumor and normal tissue after both have been exposed to the same radioactive material. This method can determine gains and losses in DNA in the region of the tumor, detecting alterations that have caused the cancer. The developing science of proteomics studies specific proteins in cells and may someday be able to provide detailed assessment of cancer cells.

Treatment

The aim of cancer treatment is to remove or destroy all or as much of the primary tumor as possible and to prevent its recurrence or metastases. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment. If the cancer is highly aggressive and cure is not likely, treatment will be aimed at relieving symptoms and controlling the cancer for as long as possible.

Cancer treatment is always tailored to the individual. The treatment choice depends on the type and location of cancer, the extent to which it has already spread, and the age, sex, and general health status of the individual. The major types of treatment are: surgery, radiation, chemotherapy , immunotherapy, hormone therapy, and bone-marrow transplantation.

Advances in molecular biology and cancer genetics have contributed greatly to the development of therapies that provide cell-targeted treatment. Genetic testing uses molecular probes to identify gene mutations that have been linked to specific cancers. In the early 2000s ongoing research is focused on new treatment and prevention methods, including molecular-targeted therapies, virus therapy, immunotherapy, and drug therapy that stimulates the self-destruction of cancer cells (apoptosis).

Targeted molecular therapy, although as of 2004 still the subject of concentrated research, was being used effectively in pediatric study subjects where it has been shown to reduce the toxicity seen with conventional chemotherapy. Unlike chemotherapy, which treats all cells uniformly, targeted molecular therapy can focus on selected cells without affecting normal cells and tissues. This refinement frees children from some of the long-term toxic effects and complications that can negatively affect quality of life and survival even if the cancer is cured.

Surgery

Surgical removal of a solid tumor is most effective with small tumors confined to one area of the body. Surgery removes the tumor (tumor resection) and usually part of the surrounding tissue to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, adjoining lymph nodes are sometimes removed as well. Surgery may also be preventive or prophylactic, removing an abnormal looking area of tissue that is likely to become malignant over time. During surgery biopsies may also be performed on tissue that may be affected by metastases. Surgery is not a typical treatment for leukemia or lymphoma, which arise in the circulatory system and lymphatic systems that extend throughout the body. Children with osteosarcoma (bone cancer) and other solid tumors are candidates for surgery, however.

Surgery may be performed in conjunction with radiation (cytoreductive surgery) or chemotherapy. The surgeon removes as much of the cancer as possible and the remaining area is treated with radiotherapy or chemotherapy or both. In advanced metastatic cancer when cure is unlikely, palliative surgery aims at reducing symptoms. Debulking surgery, for example, removes part of a tumor that is pressing on other organs and causing pain. In tumors that are dependent on hormones, one option is to remove organs that secrete the hormones.

Radiation therapy

Radiation kills tumor cells and is used alone when a tumor is in a poor location for surgery. More often, it is used in conjunction with surgery and chemotherapy. Radiation can be either external or internal. External radiation is aimed at the tumor from outside the body. In internal radiation (brachytherapy), radioactive liquid or pellets are delivered to the cancerous site via a pill, injection, or insertion in a sealed container.

Chemotherapy

Chemotherapy is the administration of drugs that kill cancer cells (cytotoxic drugs). It destroys hard-to-detect cancer cells that have spread (metastasized) through the circulation or lymph system. Chemotherapeutic drugs are given orally or intravenously, either alone or in conjunction with surgery, radiation, or both. When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or neoadjuvant chemotherapy. Because the cancer cells have not yet been exposed to anti-cancer drugs, they are especially vulnerable, allowing neoadjuvant therapy to effectively reduce tumor size. However, the toxic effects of neoadjuvant chemotherapy may be severe, because normal cells are also destroyed. Chemotherapy may also make the body less tolerant of the side effects of other treatments such as radiation therapy. Adjuvant therapy is the more common type of chemotherapy, used to enhance the effectiveness of other treatments.

Immunotherapy

Immunotherapy uses the body's own immune system, specifically a type of disease-fighting white cell called T-cells, to destroy cancer cells. Tumor-specific proteins that are part of unique genetic mutations in pediatric cancer, for example, are believed to be ideal targets for anti-tumor immune processes. Various immunological agents are as of 2004 still in clinical trials and are not as of that year widely available, though initial results are promising. Monoclonal antibodies are used to

fight cancer cells in much the same way as antibodies that are produced by the body's own immune system work to fight infection. Other substances are also being used experimentally. They include substances such as interferons, interleukins, growth factors, monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer but are designed to treat existing disease. They work by boosting the immune system and training immunized cells to destroy cancer cells.

Hormone therapy

Hormone therapy is standard treatment for cancers that are hormone-dependent and grow faster in the presence of specific hormones, such as cancer of the prostate, breast, and uterus. Hormone therapy blocks the production or action of these hormones, slowing growth of the tumor and extending survival for months or years.

Bone marrow transplantation

Bone marrow is the tissue within bone cavities that produces blood cells. Healthy bone marrow tissue constantly replenishes the blood supply and is essential to life. Sometimes drugs or radiation needed to destroy cancer cells also destroys bone marrow and only replacement with healthy cells counteracts this adverse effect. A bone marrow transplant involves removing marrow from a donor and transplanting blood-forming cells to a recipient. While not a therapy in itself, bone marrow transplantation may allow a cancer patient to undergo aggressive therapy.

Many specialists work together to treat cancer patients. The oncologist is a physician who specializes in cancer care and usually coordinates the treatment plan, directing chemotherapy, hormone therapy, and any treatment that does not involve radiation or surgery. The radiation oncologist uses radiation to treat cancer, while the surgical oncologist performs surgery to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians who treat women's and children's cancers. Radiologists read the x rays, ultrasound images, CT scans, and MRI images to help diagnose cancer. Hematologists specialize in disorders of the blood and bone marrow and are consulted in the evaluation of leukemia, lymphoma, and bone cancer.

Alternative treatment

A range of alternative treatments are available to help treat cancer that can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation. Alternative treatment of cancer is a complicated arena and a trained complementary health practitioner should be consulted.

Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain have not as of 2004 been clinically proven, many cancer patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and vomiting . Homeopathy and herbal remedies used in Chinese traditional herbal medicine also have been shown to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Prognosis

Most cancers show good cure rates if detected and treated at early stages. The prognosis involves the type of cancer, its degree of invasiveness, and the extent of metastases at diagnosis. In addition, age, general health status, and response to treatment are important factors. Cancer deaths in children have shown consistent declines, decreasing between 1975 and 2000 from 50 in 1 million diagnosed to 25 in 1 million. However, cancer is the leading cause of death among children and adolescents, responsible for 2,700 deaths each year in the United States.

Prevention

Prevention of cancer means being aware of causes and risks, which involve a combination of genetic and environmental factors. Except for family history, specific genetic causes or an inherited predisposition are generally unknown in individuals until revealed in the diagnostic process. Known environmental causes can be avoided, however. A list of guidelines offered by nutritionists and epidemiologists from leading U.S. universities to reduce the risk of cancer includes some that may apply to children and adolescents:

• Eat plenty of vegetables and fruits, especially cruciferous vegetables such as broccoli, cauliflower, and cabbage.
• Decrease or avoid eating animal fats and red meats.
• Exercise vigorously for at least 20 minutes every day.
• Avoid excessive weight gain.
• Avoid tobacco (including second hand smoke).
• Avoid excessive amounts of alcohol.
• Avoid midday sun (between 11 a.m. and 3 p.m.) when rays are the strongest.
• Avoid risky sexual practices and multiple partners.
• Avoid known carcinogens in the environment or work place.

Certain drugs being used as of 2004 for treatment could also be suitable for prevention, at least prevention of recurrences. For example, the drug tamoxifen has been very effective against breast cancer and is in 2004 being used to prevent recurrence in breast cancer survivors. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression of or to prevent head and neck cancers. Certain studies suggest that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium.

Nutritional concerns

Certain foods, including many vegetables, fruits, and grains, are believed to offer protection against various cancers. In laboratory studies, vitamins such as A, C, and E, as well as beta-carotene found in carrots and isothiocyanate and dithiolthione compounds found in cruciferous vegetables, such as broccoli, cauliflower, and cabbage, have been shown to provide protection against certain types of cancer. Studies have shown that eating a diet rich in fiber as found in fruits, vegetables, and whole grains can reduce the risk of colon cancer.

KEY TERMS

Benign —In medical usage, benign is the opposite of malignant. It describes an abnormal growth that is stable, treatable, and generally not life-threatening.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.

Bone marrow —The spongy tissue inside the large bones in the body that is responsible for making the red blood cells, most white blood cells, and platelets.

Carcinogenic —A substance that can cause cancer to develop.

Chemotherapy —Any treatment of an illness with chemical agents. The term is usually used to describe the treatment of cancer with drugs that inhibit cancer growth or destroy cancer cells.

Epithelium —The layer of cells that covers body surfaces, lines body cavities, and forms glands.

Hormone therapy —Treating cancers by changing the hormone balance of the body, instead of by using cell-killing drugs.

Immunotherapy —A mode of cancer treatment in which the immune system is stimulated to fight the cancer.

Malignant —Cells that have been altered such that they have lost normal control mechanisms and are capable of local invasion and spread to other areas of the body. Often used to describe a cancer.

Metastasis —A secondary tumor resulting from the spread of cancerous cells from the primary tumor to other parts of the body.

Radiation therapy —A cancer treatment that uses high-energy rays or particles to kill or weaken cancer cells. Radiation may be delivered externally or internally via surgically implanted pellets. Also called radiotherapy.

Sore —A wound, lesion, or ulcer on the skin.

Tumor —A growth of tissue resulting from the uncontrolled proliferation of cells.

Parental concerns

A diagnosis of childhood cancer raises many uncertainties and concerns for parents, including how to acquire the most effective therapy. Advances in molecular and cellular technologies have improved both the diagnosis and treatment of pediatric cancer and also carry with them the possibility of someday curing and preventing cancer in children. While cancer was at one time nearly always fatal in children, as of 2004 more than 75 percent of children diagnosed with cancer enjoyed disease-free survival. Targeted molecular therapy and immunotherapies are the ongoing focus of concentrated research, and studies using these cell-selective technologies in treating children have shown encouraging results, both in earlier responses and reduced toxicity and complications longer term. Parents can be assured of access to the current knowledge base in molecular biology and advanced treatment technologies that promise better outcomes.

See also Leukemias, acute; Leukemias, chronic.

Resources

BOOKS

Janes-Hodder, Honna, et al. Childhood Cancer: A Parent's Guide to Solid Tumor Cancers, 2nd ed. Cambridge, MA: O'Reilly Media Inc., 2002.

Woznick, Leigh A., and Carol D. Goodheart. Living with Childhood Cancer: A Practical Guide to Help Families Cope. Washington, DC: American Psychological Association (APA), 2002.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, NE, Atlanta, GA 30329. Web site: <www.cancer.org>.

Cancer Research Institute (National Headquarters). 681 Fifth Avenue, New York, NY 10022. Web site: <www.cancerresearch.org>.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, MD 20892. Web site: <wwwicic.nci.nih.gov>.

National Children's Cancer Society. 1015 Locust Suite 600, St. Louis, MO 63101. Web site: <www.nationalchildrenscancersociety.com>.

WEB SITES

"Childhood Cancer." Kid's Health, 2004. Available online at <www.kidshealth.org/parent/medical/cancer/cancer.html> (accessed December 8, 2004).

L. Lee Culvert Rosalyn Carson-DeWitt, MD Teresa G. Odle

Cancer

To many people, the word cancer is synonymous with death; however, that is not the reality. In industrialized countries cancer mortality rates have slowly and progressively declined between 1950 and 2000. In 2000 overall cure rates reached approximately 50 percent. Nevertheless, cancer remains the second leading cause of death in industrialized countries and a rapidly increasing cause of death in developing countries.

The scope of the problem in the United States is large. Some 1.2 million people were diagnosed with potentially fatal cancer in the year 2000. Of these, 59 percent were expected to live for at least five years (in some, the cancer may be continuously present for more than five years) with or without evidence of cancer. People of all ages, from birth to advanced age, can manifest cancer, making it the second-leading cause of death in the United States. In children cancer is unusual, but it has consistently been the leading cause of death from disease. As mortality rates from cardiovascular disease decline, the proportion of cancer deaths increases. It is anticipated that the mortality rate from cancer will surpass that from heart disease by the year 2050. Direct and indirect financial costs of cancer in the United States for the year 2000 were $178 billion.

Developing countries represented 80 percent of the world's approximately 6 billion people in the year 2000. In these countries, cancer has grown from a minor public health issue in the early 1990s to a rapidly expanding problem by the beginning of the twenty-first century. The emergence of a middle class, with attendant changes in lifestyle, increased longevity and exposure to potential carcinogens, and expectations of improved medical delivery systems have fueled the growing impact of cancer in the third world. The financial resources and socio-medical infrastructure needed to diagnose and treat, much less screen and prevent these cancers, are lacking in the developing world.

A controversial issue in the United States is whether there has been progress in the "War on Cancer" declared by Congress in 1971. Since then a large flow of tax dollars has been directed to basic and clinical research with the goal of eliminating cancer. Mortality rates from all forms of cancer have declined slightly from 1990 through 2000, but with large variations among different types of cancer. Optimistic explanations include significant improvements in treatment and prevention. More pessimistic analyses suggest that some of the more common cancers can be diagnosed earlier so that benchmark five-year mortality rates have diminished, but that the actual course of the disease is unaffected because treatments are not really more effective.

Biology

Cancer is a disease whereby the genes regulating individual cell behavior and interactions with other cells malfunction. It is therefore a "genetic" disease, although not necessarily "inherited." Cancers clearly traced to inherited susceptibility are unusual, accounting for fewer than 10 percent of cases. Rather, the majority of cancers seem to result from complicated interactions between the environment and "normal" cells.

The routine operations of cell growth, division, cell-to-cell communication, and programmed cell death (apoptosis) are complex and must be tightly controlled to preserve the integrity of the organism. Chromosomes, which contain DNA molecules organized into genes, control these regulatory processes. Similar mechanisms are present in all animals and plants, are highly conserved through evolution, and so must provide significant survival benefit. The phenomenon of cancer is infrequent in wild animals and has only come to prominence in human beings since 1900. These statistics suggest that interactions of environmental agents with the genes result in fixed alterations that eventually manifest themselves as cancer. Public health measures have increased longevity so that the progressive, possibly inherent deterioration of regulatory functions accompanying aging allows less effective repair of chronic genetic damage.

Although no single cause has been or is likely to explain all of cancer, research has demonstrated that environmental factors predominate in the development of most cancer. Proven causes of DNA damage leading to malignant change include viruses, radiation, and chemicals. Viruses such as Epstein-Barr, HIV, and papilloma can contribute to cancer development (carcinogenesis). Both therapeutic and normal environmental exposure to radiation increase the risk of cancer. Multiple chemicals have been linked to cancer, of which the best examples are the constituents of tobacco. How these and other unknown environmental factors, particularly dietary and airborne, interact with human genes to cause irreversible, malignant transformation is the subject of intensive research.

Malignant cells can multiply and divide in the tissue of origin and can travel through the circulatory system and create secondary deposits (metastases) in vital organs. These capabilities underlie the phenomena of invasive lumps (tumors) and the potential for the dissemination of cancer. Most cancer cells, whether at the primary or secondary site, divide at about the same rate as their cells of origin. Malignant cells, however, do not typically undergo normal programmed cell death (apoptosis) and consequently accumulate. Most often, the cause of death in cancer is a poorly understood wasting process (cachexia).

Prevention and Screening

Prevention of cancer, or the reduction of risk for a person who has never experienced the disease, is a desirable goal. For those cancers resulting from known environmental exposures, such an approach has been most successful. Avoidance of tobacco products is no doubt the best proven means of preventing cancer. In industrialized countries, regulatory agencies monitor chemical and radiation exposure. Dietary habits are felt to influence the risk of developing certain cancers, but there is very little evidence that dietary manipulations lead to significant risk reduction.

Screening is the attempt to diagnose an established cancer as early as possible, usually before the onset of symptoms, in order to optimize the outcome. A screening technique is designed to simply, safely, and cheaply identify those patients who may have a certain type of cancer. If screening-test result is positive, further testing is always necessary to rule the diagnosis in or out. There is considerable controversy in this field. It cannot be assumed that early detection is always in the patient's best interest, and the overall financial costs in screening a population must be weighed against the actual benefits. Screening may be counterproductive under the following conditions:

1. Treatment is not more effective with early detection.
2. The patient will die of an unrelated condition before the diagnosed cancer could be troublesome or fatal.
3. The screening examination can be harmful.
4. The screening examination is falsely "negative" and thus falsely reassuring.
5. The treatment causes complications or death in a patient in whom the cancer itself would not have led to problems.

In spite of these limitations, there have been successes. Good evidence exists that not only early detection but also improved survival can be achieved in breast, cervical, and colorectal cancers. With minimal danger and cost, appropriate populations screened for these diseases benefit from reduced mortality. Prostate cancer, however, is more problematic. Measurement of prostate-specific antigen (PSA), a substance made by both normal prostate as well as malignant prostate cells, can identify a patient with prostate cancer before any other manifestations. But because of the relatively elderly population (often with unrelated potentially serious conditions) at risk, it has been difficult to prove that treatment confers a quantitative or qualitative benefit. Continued efforts will be made to create screening techniques that truly allow more effective treatment for cancers detected earlier.

Diagnosis and Treatment

Once a malignancy is suspected, tests (usually imaging techniques, such as X rays, ultrasounds, nuclear medicine scans, CAT scans, and MRIs) are performed for confirmation. Ultimately a biopsy, or removal of a piece of tissue for microscopic examination, is necessary for determination of the presence and type of cancer. Staging tests reveal whether the disease has spread beyond its site of origin. Because of the inability of current techniques to detect microscopic deposits of cancer, a cancer may frequently appear to be localized but nevertheless exist elsewhere in the body below the threshold of clinical detection.

The diagnostic and staging process should permit the optimal clarification of the goals of treatment. Curative treatment intends permanent elimination of cancer, whereas palliative treatment intends to relieve symptoms and possibly prolong life. In every cancer situation there are known probabilities of cure. For example, a specific patient with "localized" breast cancer may have a 50–60 percent chance of cure based on predictive factors present at the time of diagnosis. Follow-up "negative" tests, however, do not yield the certainty that there is no cancer, whereas the documented presence of recurrent cancer has clear significance. Cancer, indeed, is the most curable of all chronic diseases, but only the uneventful passage of time allows a patient to become more confident of his or her status.

Surgery is the oldest and overall most effective cancer treatment, particularly when tumors appear to be localized and cure is the goal. It is a preferred modality for breast, prostate, skin, lung, colon, testicular, uterine, brain, stomach, pancreas, and thyroid tumors. The aims of cancer surgery include elimination of as much cancer as possible, preservation of organ function, and minimal risk and suffering for the patient. Occasionally surgery is intentionally palliative, particularly when other treatment modalities are added in an effort to improve symptoms.

Radiation therapy has been a mainstay of cancer treatment since the 1940s, when doctors first began to understand its potential benefits and short and long-term risks. Therapeutic ionizing radiation is generated by a linear accelerator and delivered externally to a well-defined area. It thus shares with surgery an advantage for localized tumors. The inherent differences in radiation sensitivity between malignant tissues and the surrounding normal tissues permits the exploitation of radiation for therapeutic benefit. When the cancerous tissue is less sensitive to radiation than the normal tissues, radiation can cause more harm than good. Radiation has been a useful primary treatment modality in tumors of the head and neck, lung, cervix, brain, pancreas, and prostate. For tumors that have metastasized to tissues such as bone and brain, radiation has been very useful for palliative purposes.

Systemic treatments, either by themselves or in concert with surgery and/or radiation, offer the most rational options for a disease, which so often has spread before diagnosis. The ideal treatment would be a substance that travels throughout the body, neutralizes every cancer cell, but causes no harm to any normal cell. Research has not yet yielded such a completely specific and non-toxic substance.

The 1950s saw the advent of anticancer drugs that came to be known as "chemotherapy." By the year 2001 approximately sixty chemotherapy drugs became commercially available. In general these drugs cause irreversible cell damage and death. They tend to be more destructive to rapidly dividing cells and so take their heaviest toll on relatively few malignancies as well as predictability on normal tissues (mucous membranes, hair follicles, and bone marrow). For some very sensitive disseminated cancers such as testicular, lymphomas, and leukemias, chemotherapy can be curative. For many others, such as advanced breast, ovarian, lung, colon cancers, chemotherapy may offer palliative benefits. Since the 1980s chemotherapy has played an important role in the multimodality treatment of localized breast, colon, lung, and bladder tumors. Except for curable and highly chemosensitive malignancies, chemotherapy kills at most 99.99999 percent of cells, but with a burden of trillions of cancer cells, millions of resistant cells remain. Even using high-dose chemotherapy, it appears that by the year 2001 chemotherapy may have reached a plateau of effectiveness.

Insights into the basic genetic, molecular, and regulatory abnormalities of malignant cells have opened up entirely new systemic approaches. "Natural" substances such as interferons and inter-leukins have therapeutically modulated cell proliferation and led to regression of some tumors. Antiangiogenesis agents interfere with the malignant cell's need for accessing new blood vessels. Chemicals designed to inhibit the inappropriate production of growth factors by malignant cells have been synthesized and show promise. Monoclonal antibodies aimed at proteins concentrated on the malignant cell's surface have achieved tumor shrinkage. By the year 2000 the thrust in basic cancer research had focused on manipulation of the fundamental processes that allow malignancies to grow and spread.

The Internet has allowed patients, families, and medical providers rapid access to information previously obtainable only through libraries or physicians. Such information, however, may be unfiltered, unsubstantiated, and misleading. Even when the information is correct, consumers may be unable to process it properly because of fears concerning their condition. All observers agree, however, that this form of communication will rapidly affect cancer research and treatment.

"Complementary" or "alternative" modalities have existed for many years and represent nonscientific means of attempting to cure or palliate cancer. The multitude of available products and techniques is enormous: herbal extracts, vitamins, magnetic therapies, acupuncture, synthetic chemicals, modified diets, and enemas. The vast majority of these have never been evaluated in a rigorously controlled scientific way that would allow more definitive and precise evaluation of their benefits and risks. Nevertheless, evidence has shown that as many as 50 percent of all cancer patients, irrespective of treatability by conventional methods, try at least one form of complementary medicine. Some proponents feel that these treatments should serve as adjuncts to conventional ones, while others feel that all conventional treatments are toxic and should be replaced by alternative ones. To investigate the potential of these approaches, the National Institutes of Health established the Institute of Alternative Medicine in 1996.

End-of-Life Care

Because approximately 50 percent of cancer patients will die from their cancer, management of their dying takes on great importance. In the 1980s and 1990s multiple studies demonstrated that such basic concerns as pain and symptom control, respect for the right of the individual to forego life-prolonging measures, and spiritual distress have been mismanaged or ignored by many health care providers. In spite of the emergence of the modern hospice movement and improvements in techniques of symptom alleviation, most cancer patients die in hospitals or in nursing homes while receiving inadequate palliative care. The American Society of Clinical Oncology (ASCO) in 1998 mandated that part of fellowship training for oncologists include the basics of palliative care in order to rectify these problems.

See also: Causes of Death; Pain and Pain Management; Symptoms and Symptom Management

Bibliography

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Burns, Edith A., and Elaine A. Leventhal. "Aging, Immunity, and Cancer," Cancer Control 7, no. 6 (2000):513–521.

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Groopman, Jerome. "The Thirty-Years War." The New Yorker, 4 June 2001, 52–63.

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Internet Resources

American Cancer Society. "Statistics." Available from www.cancer.org.

JAMES BRANDMAN

CANCER

Cancer is the end product of a multistep process (carcinogenesis) that occurs over many years. The term "cancer" actually refers to numerous distinct diseases characterized by abnormal cell growth and differentiation. Cancers are categorized by the organ and/or cell of origin. For example, squamous cell carcinoma of the lung arises from pulmonary epithelial tissue, whereas adenocarcinoma of the breast arises from mammary duct epithelium. The natural history of a cancer is highly dependent on the organ and cell type from which it is derived. In addition, prognosis is influenced by the stage and histologic grade of the cancer. Staging is generally designated by the TNM (tumor, nodes, metastasis) staging system, which takes into account the size of the primary tumor(T), the extent to which local lymph nodes (glands) are involved (N), and whether or not distant metastases are present (M). The histologic grade, determined by microscopic examination of the biopsy specimen, provides an objective assessment of the degree of cellular differentiation.

INCIDENCE, PREVALENCE, AND MORTALITY

The worldwide burden of cancer is a major health problem, with more than 8 million new cases and 5 million deaths per year. The burden from cancer may be described in terms of incidence (number of new cases per 100,000 each year), prevalence (number of people at a given point in time with a cancer diagnosis), and mortality (number of cancer deaths). With few exceptions, cancer incidence, prevalence, and mortality rates are higher in industrialized countries (e.g., United States, European nations) than in developing countries (e.g., African nations, China). Incidence rates for specific cancers can be dramatically affected by the use of screening procedures to identify asymptomatic disease. This is illustrated by the dramatic increase in the incidence of prostate cancer that accompanied the introduction of prostate-specific antigen (PSA) screening in the late 1980s. Similarly, prevalence rates may be a poor index for comparing cancers, because they are dependent upon incidence, natural history, and treatment efficacy. For example, due to the relatively short life expectancy of individuals with pulmonary neoplasms, the prevalence of lung cancer is much lower than that of prostate cancer, despite the higher mortality rates associated with lung cancer. In addition to the impact of screening and natural history, prevalence rates increase as treatment improves, because therapeutic advances enable individuals to live longer following a cancer diagnosis.

Worldwide, lung cancer is the leading cause of cancer mortality, followed by stomach cancer. Smoking remains the leading preventable cause of cancer, and mortality and incidence rates of lung cancer rise and fall with smoking rates. The current trend shows a leveling off of smoking-related cancers in developed countries, possibly because of health-promotion and disease-prevention efforts. Geographical variations occur in cancer incidence and mortality, with Africa and Asia generally having lower rates than North America and Europe. However, it has been noted that differences in data collection and diagnostic practices make worldwide cancer comparisons somewhat difficult. Overall, worldwide incidence rates of breast, colon and rectum, and prostate cancers are highest in developed countries, while cancers of the cervix, mouth and pharynx, esophagus, and liver are higher in developing countries. Migration studies generally report that migrants from developing countries to developed countries adopt cancer incidence rates equivalent to those of their new country. For example, studies of Japanese and Chinese immigrants living in the United States show that their risks for prostate and breast cancers increase dramatically the longer they reside in the United States. Similar trends for increased risk are seen among African immigrants in European countries. Geographical variations in cancer incidence and mortality also exist in the United States. Each cancer site shows some variation, such as higher prostate cancer mortality rates in the South Central and southern Atlantic states, and higher breast cancer mortality rates in the northeastern states. The Atlas of United States Mortality, published by the Centers for Disease Control and Prevention, provides detailed geographic information on cancer mortality rates in the United States, and is available online at http://www.cdc.gov/nchs/data/atlasmet.pdf.

In the United States, cancer is the second leading cause of death; although there has been a slight decline in the number of people dying from cancer since 1990, with more than one-half of those who develop cancer being cured or surviving for over five years. Because cancer is many diseases, some cancers are more common and/or more curable than others. For example, although nonmelanoma skin cancer, mainly caused by overexposure to ultraviolet (UV) radiation from the sun, is responsible for the largest number of new cancer cases each year, mortality rates associated with it are low.

Incidence, prevalence, and mortality in the United States vary by cancer site, between whites and blacks, and between men and women. By order of incidence, the three most common cancers in men are prostate, lung, and colorectal; in women the three most common cancers are breast, lung, and colorectal. These cancer sites represent more than one-half of both new cases of cancer and deaths from cancer each year. Lung cancer is the leading cause of death from cancer for men and women, accounting for almost one-third of cancer deaths.

Although cancer risk increases with age, malignant diseases are an important cause of morbidity and mortality in the pediatric population. The most frequent cancers in children are leukemias, tumors of the nervous systems, lymphomas, soft-tissue sarcomas, and kidney tumors. Other than lung cancer, which increases dramatically after age forty, three out of every four deaths from cancer occur in individuals older than sixty years of age.

CAUSES OF CANCER

Environmental and lifestyle factors such as tobacco use, diet, alcohol consumption, and exposure to sunlight play a primary role in the development of the majority of cancers. In addition, exposure to occupational factors and to specific pathogens (e.g., viruses, bacteria), hormones, and radiation also contributes to cancer at particular sites. However, the question still remains as to why one person exposed to a given environmental or lifestyle risk factor develops cancer and another person does not. The importance of hereditary factors (gene-environment interactions) cannot be overemphasized in this regard. True "hereditary cancers," those attributable to specific genes that are passed from one generation to another, account for only a small proportion of cancer cases, however.

Exposure to carcinogens in tobacco smoke accounts for almost one-third of cancer cases, especially cancers of the lung, respiratory tract, esophagus, bladder, pancreas, and, most likely, cancers of the stomach, liver, and kidneys. Carcinogens found in the environment and the workplace (e.g., asbestos, benzene, vinyl chloride compounds, dyes, arsenic, petroleum products) and cancers associated with exposure to these chemicals (e.g., lung and bladder) are higher in urban areas than in rural areas. Diet also influences the risk of cancer, although researchers are unsure of the mechanisms involved. In general, evidence supports an increased risk of various cancers (e.g., colon, rectum) with a high intake of red meats, and a decreased risk of various cancers (e.g., lung, colon, stomach) with a high intake of vegetables and fruits. Other food constituents, such as vitamins and minerals, are also being investigated for their ability to prevent cancer.

Other possible causes of cancer include pathogens, such as hepatitis B and C viruses in liver cancer, and the Helicobacter pylori bacterium in stomach cancer. Hormonal factors contributing to cancer have focused on estrogen, progesterone, and testosterone, and their role in reproductive organ cancers. These steroid hormones are being investigated because they influence the growth of cells, particularly those of the prostate, ovary and cervix, and breast. Radiation exposure, especially UV radiation from the sun, is a significant contributor to cancer of the skin, and using sunscreens has been shown to reduce skin cancer risk.

Interactions between genes and environmental exposures are of great importance in determining one's risk of developing cancer. For instance, genes and nutrients can interact to increase or decrease the risk of cancer depending on genetic variations known as polymorphisms—different forms of the same gene that may either increase or decrease the risk of cancer. For example, different polymorphisms in the gene that determines how vitamin D is metabolized can influence the risk of prostate cancer; one polymorphism is associated with increased risk of prostate cancer and another is associated with decreased risk. Polymorphisms in the genes that are responsible for repairing radiation damage to skin cells also play a role in increasing or decreasing cancer risk.

CANCER PREVENTION AND TREATMENT

Many cancer risk factors are avoidable. Preventing cancer by attention to diet and by quitting or never starting smoking are the most significant strategies to reduce cancer risk. Prevention of cancer is being investigated in clinical trials on dietary patterns (high intake of vegetables and fruits; low intake of saturated fats) and dietary constituents such as vitamins, minerals, and soy. Future progress may depend partly on strategies such as chemoprevention—the use of natural or synthetic substances to prevent cancer cells from forming, progressing, or recurring. For example, the antiestrogen hormone tamoxifen has been shown to reduce the risk of developing breast cancer by 50 percent among women at high risk for this disease. It also has been shown to reduce the risk of developing a new primary breast cancer in the opposite breast among women with a history of breast cancer. Chemopreventive agents also are being investigated for prevention of colon, rectum, prostate, and lung cancers.

SCREENING AND EARLY DETECTION

Mammography has been shown to reduce breast cancer mortality among women over the age of fifty, and Pap smear screening has dramatically reduced mortality from cervical cancer. In addition, there is growing evidence that fecal occult blood testing and endoscopic screening significantly reduce mortality from colorectal cancer. Identification of mutations is becoming an important tool for identifying individuals at high risk of various cancers. For instance, DNA repair-gene mutations (e.g., MSH2, PMS1) have been associated with a higher risk of colon cancer, as have mutations in the tumor suppressor genes BRCA1 and BRCA2 in breast cancer. Although it is believed that inherited risk for cancer accounts for a small proportion of total cancer cases each year, identifying this risk may help researchers determine how cancer develops and progresses, and may provide a tool for targeting prevention or treatment strategies.

Prognosis is dependent on the type of cancer diagnosed, the stage of the disease at the time of diagnosis, and the effectiveness of currently available therapy. Surgery, radiation, chemotherapy, hormonal therapy, and immunologic therapy form the basis of modern cancer treatment. Surgery is generally the treatment of choice for localized tumors, although radiation often is an appropriate alternative. Lasers are being used for small noninvasive tumors of the skin, cervix, and throat. Radiation therapy is often recommended as primary therapy (e.g., for Hodgkin's disease and early stage tumors of the head and neck), and is an important adjunct to lumpectomy for the treatment of breast cancer. Radiation therapy also plays an important role in the symptomatic management of patients with advanced cancer (e.g., bone or brain metastases). In contrast to surgery and radiation, chemotherapy is a systemic, rather than local, therapy, because the drugs are distributed throughout the body. Chemotherapy generally is required to treat advanced cancers that are not amenable to surgical removal or radiation therapy. Chemotherapy is often used after surgery (adjuvant therapy) to reduce the risk of relapse. The most common indication for adjuvant chemotherapy is following surgery for localized breast or colorectal cancer.

Hormone therapy represents a very important category of cancer treatment for breast cancer (tamoxifen and raloxifene) and prostate (androgen blockers) cancer. In addition, immunotherapy (also called biologic therapy) is being used to boost the immune system to fight cancer cells. Monoclonal antibodies are one type of immunotherapy that can be used to fight specific cancer cells or to carry chemotherapeutic agents to a tumor. Interferon is another immunotherapy that has shown promise in slowing the growth of tumors. Each of these treatments has advantages and disadvantages, and should be discussed with a physician.

CANCER IN DEVELOPING COUNTRIES

Cancer trends are of great concern to the public health community. As developing countries become more industrialized, incidence and mortality rates for cancers of the breast, colon, rectum, and prostate begin to rise. Also, smoking is increasing worldwide—along with lung cancer incidence and mortality rates. Liver cancer shows the same trends as lung cancer, but for a different reason. Infection with the hepatitis B or C viruses is a major risk factor for liver cancer. In some countries, where a vaccine for hepatitis B is widely used to vaccinate infants, liver cancer incidence in later life has declined; however, incidence rates in developing countries, where vaccination is not widely available, appear to be increasing. Another virus, the human papillomavirus (HPV), is an important risk factor for cervical cancer. Cervical cancer and HPV are more common in equatorial countries (e.g., in Latin America, sub-Saharan Africa, and Southeast Asia) and less common in countries in northern latitudes. Screening and treatment for early stages of cervical cancer have made significant inroads for reducing the incidence and mortality of this disease.

Howard L. Parnes

Darrell Anderson

(see also: Breast Cancer; Carcinogen; Cervical Cancer; Colorectal Cancer; Environmental Determinants of Health; Environmental Tobacco Smoke; Genetics and Health; Geography of Disease; Geriatrics; Incidence and Prevalence; Lung Cancer; Melanoma; Mortality Rates; Nutrition; Occupational Safety and Health; Oral Cancer; Ovarian Cancer; Prevention; Preventive Health Behavior; Prostate Cancer; Screening; Skin Cancer )

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CANCER

The Most Dreaded Disease

For Americans in the 1950s, there was no diagnosis of illness more feared than cancer. Heart disease killed twice as many people annually, but it did not cause the pain or fear of malignant tumors. In 1958 Science Digest reported that there were 450,000 new cases of cancer diagnosed each year and that at any one time about seven hundred thousand cases of cancer were being treated in America. In 1958, according to Patterns of Disease, a publication by Parke, Davis, one woman in four under the age of thirty-five could expect to get cancer, and one in seven would die from it; one man in five under the age of fifty would be afflicted, and one in eight would die.

Focusing Attention

At the beginning of the 1950s some physicians considered cancer to be incurable, and many hospitals considered it their duty to guard their cancer patients from intrusions by researchers. Two groups changed that attitude and focused health attention during the decade on cancer. The American Cancer Society devoted enormous energy to the fight against the disease. Its high-visibility fund-raising campaign heightened public optimism that cancer was curable, concentrated the attention of the public on early detection, and provided much-needed money for research.

The Government Response

The government, through the National Cancer Institute, made a commitment to eradicate the disease as well. In 1953 a cancer research hospital was opened at the National Institutes of Health Complex in Bethesda, Maryland. That same year the National Institutes of Health, acting on the instructions of Congress, began a concentrated effort to find a cure for leukemia, a malignancy of blood cells that often strikes children. With the active lobbying support of the private American Cancer Society, the National Cancer Institute budget rose from $4 million in 1947 to $110 million in 1959.

Cancer Detection

On 1 January 1950 there were 134 special cancer-detection centers in the United States, approved by the American College of Surgeons (ACS), where a person could go for inexpensive cancer screening. The initial screening fee was ten dollars for tests that would cost twenty-five dollars to one hundred dollars in a doctor's office. (By the mid 1950s the screening fee had gone up in some centers to twenty dollars.) Initial screening consisted of a series of tests, sometimes with unpronounceable names—cytological smears, tests in which body fluids or cast-off cells are examined under a microscope to search for cancerous or precancerous cell formations; sigmoidoscopies, in which the colon is inspected for abnormalities; chest X-rays to search for growths; and breast examinations, especially for women. Everyone over the age of thirty-five was advised to undergo cancer screening once a year.

Cancer and Women

By 1952 women were advised to visit a gynecologist, rather than a family doctor, for a properly administered Pap smear (a cytological test named for George Papanicolaou to identify cervical cancer). The American Cancer Society prepared a film, distributed at no cost to women's groups, to demonstrate how women could examine their own breasts for suspicious lumps, which the ACS advised be done monthly.

The Cost of Cancer

In addition to its emotional cost, a diagnosis of cancer indicated the need for very expensive treatment and usually prolonged hospitalization. By 1958 cancer patients paid $300 million annually in hospital bills, and, according to the National Cancer Institute, the disease was calculated to cost the nation over $12 billion a year, including direct costs of treatment and lost productivity of workers. There were basically three types of cure: surgery, in which the malignancy was cut out; radiotherapy, in which the malignant cell growths were subjected to radiation in an attempt to kill them; and the newest treatment, chemotherapy, in which a medicine was taken to attack the malignancy.

Surgery

The most common response to cancer in the 1950s was surgical removal, but it was an expensive, imperfect cure that often debilitated patients. The surgical cure for cancer of the larynx, for example, left victims without a voice and able to communicate only by training that taught them to gulp air and belch it out to form a sound. Statistics showed in 1958 that most cancers grew for two to three years before symptoms appeared and that most people waited six months to a year before seeing a doctor when they detected symptoms. By then it was often too late for surgery. Even when surgery was performed, there was always the question of whether all of the cancerous cells were removed. If some were missed, a recurrence could be expected.

WHAT IS CANCER?

Cancer is a very general word used to indicate many malignant diseases that may have only the vaguest relationship. Generally a cancer is an invasive group of cells that grow uncontrollably. Eventually cancer cells may spread into the territory of healthy cells critical to the operation of the body and kill or disable them. Cancers strike in many different ways; they react differently to medical treatment; and they have different growth patterns. They tend to have one grim characteristic in common, though: they usually kill. Taken together cancers have long been the second most common cause of death in America after heart disease. In 1950, 204,000 people died of cancer, accounting for about 14 percent of all deaths in the country.

CANCER QUACKS

In his book The Truth about Cancer (Prentice-Hall, 1956) Dr. Charles Cameron identified three types of cancer quacks: the dumb quack, "who knowing nothing at all about cancer, yet believes that it will yield to the secret formula which he alone possesses"; the deluded quack, who may be educated and is sometimes even a doctor, "but his knowledge of cancer is scanty, and his understanding of research methods is strictly limited"; and the dishonest quack, "far and away the commonest type.… He is in the business of treating cancer for one reason only—to make a killing, which he often does, both ways."

Among the quack cures are pastes or poultices to "draw the cancer out," secret potions that destroy the cancer, and eccentric diets to starve the cancer. One quack recommended a poultice of red cabbage to entice the cancer to the surface of the skin and a diet of the same red cabbage, ostensibly to push from the inside. One secret medicine was found to include water, vinegar, fly specks, and insect wings; another called "glyoxylide" omitted the extras—it was simply water. Quack diets included the grape-diet cure, in which the patient choked down grapes all day long; a diet of lettuce, liver, fruit juice, and vitamins to the exclusion of meat, eggs, and what Dr. Cameron calls "other staples of balanced fare." One quack raided by the Food and Drug Administration used a machine that consisted of "a senseless jumble of wires" to cure the cancer.

The tragedy, of course, is that the quacks kept patients from real doctors who could treat them as effectively as modern medicine knew how. The quacks took extorted money from terminally ill people and in return denied them whatever hope the golden age of medicine had to offer. For a portrait of the most celebrated of the cancer quacks, see the entry in this chapter on Harry Hoxsey.

Preventive Surgery

Cancer surgery in the 1950s was not limited to patients who had been diagnosed as having malignancies. Many surgeons in the 1950s advocated the preventive removal of women's reproductive organs after they had passed childbearing age, because the incidence of uterine and cervical cancer increased for them, but some doctors found that practice unethical, even if it was widespread. In 1953 the American Medical Association Journal estimated that as many as two-thirds of all hysterectomies (the surgical removal of a woman's uterus) were unnecessary.

Radiotherapy

Radiation kills cells and can be focused on a selected spot that may be unreachable by surgery without damaging vital organs. Radiotherapy was still being developed during the 1950s, but it was widely used nonetheless to attack malignant tumors. One system of exposing tumors to radiation was to implant radioactive seeds in the cancerous mass. The seed would kill the tumor in time.

Rays

The most common form of radiotherapy was administered by huge machines such as the two-million-volt X-ray machine developed by Massachusetts Institute of Technology scientists for use beginning in 1953 by cancer specialists at Massachusetts General Hospital in Boston, the 450-million volt synchrocyclotron at the Argonne Cancer Research Hospital in Chicago, and the powerful cobalt-ray machine that could produce as much energy as a $100 million chunk of radium. These machines consisted largely of imposing tubes, sheathed in lead to prevent radiation from escaping, that projected radioactive rays to a designated focal point. Often the patient sat on a turntable so that the rays concentrated on some internal spot in the body could pass through outer tissues in diminished concentrations.

CANCER SYMPTOMS

In an effective series of public-service announcements in the 1950s, the American Cancer Society risked offense to squeamish people by providing a plain-language list of early symptoms of cancer that should cause a patient to contact his or her physician immediately:

Any lump, especially in the breasts;

Unusual bleeding or discharge from nipples, vagina or rectum;

Spitting of blood;

Persistent indigestion or difficulty in swallowing;

Any lasting change in normal bowel habits;

Passage of black stools;

Unexplained weight loss;

Changes in color or size of a mole or wart;

Any sore that does not heal properly;

Persistent hoarseness or cough.

Source:

Consumer Reports Buying Guide Issue, 1956.

Chemotherapy

Not yet fully developed during the 1950s, chemotherapy nonetheless seemed to many specialists the most promising of the available cancer treatments. At multimillion-dollar labs, such as Dr. Selman Waksman's $2.5 million Microbiology Research Center at Rutgers University in New Brunswick, New Jersey, researchers tried thousands of chemical compounds each year in the attempt to find one that would effecively cure cancer. In 1959 Dr. John R. Heller of the National Cancer Institute reported that researchers were screening compounds at the rate of forty thousand a year and had found seventy-two compounds that were promising enough to merit further testing. The trouble was that there were so many different cancers. In 1959 seventeen separate types of viruses were known to cause different types of cancer in animals, and one virus, polyoma, caused twenty-six types of cancer all by itself. At the same time, one type of virus seemed to attack cancers, and some thought was given to infecting people with a flu virus to protect them from cancer.

Cancer and the Environment

During the 1950s many people tried to dismiss the overwhelming evidence suggesting environmental causes of cancer, because the implications were so intimidating. To avoid apparent risks of cancer, people faced the prospect of changing dramatically the way they lived and of harnessing the progress and prosperity of the nation's biggest industries. Some scientists went so far as to say that cancer was the price of a middle-class American lifestyle. Tearing down the nation's industrial smokestacks and cleaning up the exhaust emissions of the seventy million registered motor vehicles in the country (as of 1959) was too radical for most Americans. People in the 1950s were not so frightened by the risk of cancer that they would radically alter their way of life to avoid it.

Cancer and Smoking

The most debated cause of cancer in the 1950s was tobacco. Researchers were able to show in 1954 that mice painted with tobacco tars developed skin cancer, and they noted that human victims of malignancies in the respiratory system were very often smokers. But the news that there is a link between smoking and cancer was not received kindly by a nation that produced over a half trillion cigarettes at the end of the decade. Smokers did not want to believe it, and manufacturers were outraged. In 1954 the American cigarette companies formed the Tobacco Industry Research Council, a high-budget, public relations organization that defended the industry against criticism from health-conscious scientists.

Results

In 1956 there were, by one report, over nine thousand original scholarly articles on cancer, and hundreds of meetings were held each year in the late 1950s to discuss the disease. The results were encouraging, but hardly as dramatic as the polio researchers could claim. By the end of the 1950s cancer specialists were beginning to understand some of the causes of malignancy, but prevention was a difficult issue. Treatment by radiotherapy and chemotherapy supplemented radical surgery, which itself became more advanced. In 1950 alone 2,500 chemicals were tested as cancer cures, and 124 of them were thought to show promise. By 1960 one patient in three was said to have been cured by surgically removing the cancerous tumor. Nonetheless, cancer was not eradicated during the 1950s, nor even close. The failure to make more headway after such a concentration of effort costing so much money was disappointing to some. But even if researchers could not cure cancer in 1959, they could sometimes treat it. Eight hundred thousand patients who had been diagnosed with cancer were alive in 1959 who would arguably not have survived the decade without the treatment modern medicine offered. Most important, these patients and their families were offered genuine hope of more effective treatment for the next generation.

THE ATOMIC HOSPITAL

The Argonne Cancer Research Hospital at the University of Chicago opened in March 1953. It was designed to conduct research in the use of radiation to treat cancer. The eight-floor hospital, which cost $4.2 million to build, was underwritten by the Atomic Energy Commission, which also provided $1 million a year for operating costs.

Among the cancer-fighting equipment in the hospital were a 450-million-volt synchrocyclotron; a 50-million-volt linear accelerator; the most powerful cobalt-ray emitter known; a two-million volt Van de Graaf generator; and a 250,000-volt X-ray machine. To protect against unwanted radiation, the two floors of patient rooms had eight-inch concrete walls and the floors were covered with an easily cleanable plastic. The Atomic Energy Commission specified that the hospital's facilities be available to the nearby Argonne National Laboratory, which conducted experiments in atomic energy, as well as many other research institutions.

Sources:

Walter C. Alvarez, "The Search for a Cure for Cancer," Good House-keeping, 146 (April 1958): 92, 248-251;

Charles S. Cameron, "Cancer Quacks Can Kill You," Science Digest, 40 (October 1956): 26-30;

"Cancer: New Methods—and Drugs—Hold High Hope," Newsweek, 43 (17 May 1954): 58, 60-61.

Cancer

Cancer is a disease characterized by the uncontrolled growth and spread of abnormal cells. Around the world, over 10 million cancer cases occur annually. Half of all men and one-third of all women in the United States will develop some form of cancer during their lifetime. It is one of the most feared diseases, primarily because half of those diagnosed with cancer in the United States will die from it. Cancer is a leading cause of death around the world, causing over 6 million deaths a year. The exact causes of most types of cancer are still not known, and there is not yet a cure for cancer. However, it is now known that the risk of developing many types of cancer can be reduced by adopting certain lifestyle changes, such as quitting smoking and eating a better diet .

Prevalence

Cancer is, in general, more common in industrialized nations, but there has been a growth in cancer rates in developing countries, particularly as these nations adopt the diet and lifestyle habits of industrialized countries. Over one million people in the United States get cancer each year. Anyone can get cancer at any age; however, about 80 percent of all cancers occur in people over the age of fifty-five.

Cancer can affect any site in the body. About one hundred human cancers are recognized. The four most common cancers in the United States are: lung, colon/rectum, breast, and prostate . Together, these cancers account for over 50 percent of total cancer cases in the United States each year.

There is a marked variation among countries in incidence of different cancers. Most of the variation in cancer risk among populations, and among individuals, is due to environmental factors, such as cigarette smoking and certain dietary patterns, that can affect one's risk of developing cancer. For example, individuals living in Australia have the highest worldwide lifetime risk of skin cancer, at over 20 percent, due to the high level of exposure to the sun of people in Australia. People in India have twenty-five times the average risk of developing oral cancer sometime during their lives due to the popularity of chewing tobacco in that country. In fact, India has the world's highest incidence of oral cancer, with 75,000 to 80,000 new cases a year. The population of Japan has the highest rates of stomach cancer in the world due to the high consumption of raw fish by the Japanese.

Types of Cancer

Cancers are classified according to the types of cells in which they develop. Most human cancers are carcinomas, which arise from the epithelial cells that form the superficial layer of the skin and some internal organs. Leukemias affect the blood and blood-forming organs such as bone marrow , the lymphatic system , and the spleen. Lymphomas affect the immune system . Sarcoma is a general term for any cancer arising from muscle cells or connective tissues.

Growth and Spread of Cancer

Cancer develops when cells in a particular part of the body begin to grow out of control. Normal body cells grow, divide, and die in an orderly way. Cancer cells, however, continue to grow and divide without dying. Instead, they outlive normal cells and continue to form new abnormal cancer cells. As most cancer cells continue to grow, they lump together and form an extra mass of tissue. This mass is called a malignant tumor.

As a malignant tumor grows, it damages nearby tissue. Some cancers, like leukemia, do not form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues, where they grow.

Cancer can begin in one part of the body and spread to others. The spread of a tumor to a new site is called metastasis. This process occurs as cancer cells break away from a tumor and travel through the bloodstream or the lymph system to other areas of the body. Once in a new location, cancer cells continue to grow out of control and form a new malignant tumor.

Causes of Cancer

The exact cause of cancer is not known. Most cancers result from permanent damage to genes or from mutations, which occur either due to internal factors, such as hormones , immune conditions, metabolism , and the digestion of nutrients within cells, or by exposure to environmental or external factors. A chemical or other environmental agent that produces cancer is called a carcinogen.

Overall, environmental factors, defined broadly to include tobacco use, diet, infectious diseases , chemicals, and radiation, are believed to cause between 75 and 80 percent of all cancer cases in the United States. Tobacco use, including cigarettes, cigars, chewing tobacco, and snuff, can cause cancers of the lung, mouth, throat, larynx, bladder, kidney, esophagus, and pancreas. Smoking alone causes one-third of all cancer deaths in the United States. Heavy consumption of alcohol has also been shown to increase the risk of developing cancer of the mouth, pharynx, larynx, esophagus, liver, and breast.

Overweight and obesity are associated with increased risk of cancers of the breast, colon, endometrium, esophagus, kidney, and gallbladder. The following chemicals have been found to cause cancer: coal tars and their derivatives, such as benzene; some hydrocarbons; aniline, a substance used to make dyes; and asbestos. Radiation from a variety of sources, including the ultraviolet light from the sun, is known to lead to skin cancer.

Several infectious agents have also been implicated in cancer. Evidence suggests that chronic viral infections are associated with up to one-fifth of all cancers. These include hepatitis B virus (HBV), which can lead to cancer of the liver; the Epstein-Barr virus, a type of herpes virus that causes infectious mononucleosis and has been associated with Hodgkin's disease, non-Hodgkin's lymphomas, and nasopharyngeal cancer; the human immunodeficiency virus (HIV), which is associated with an increased risk of developing several cancers, especially Kaposi's sarcoma and non-Hodgkin's lymphoma; and human papilloma viruses (HPV), which have been proven to cause cervical cancer and have also been associated with cancers of the vagina, vulva, penis, and colon. The bacterium Helicobacter pylori has been linked to stomach cancer.

About 5 to 10 percent of cancers are hereditary, in that a faulty gene or damaged DNA that has been inherited predisposes a person to be at a very high risk of developing a particular cancer. Two genes, BRCA1 and BRCA2, have been found to cause some breast cancers. Other genes have been discovered that are associated with some cancers that run in families, such as cancers of the colon, rectum, kidney, ovary, esophagus, lymph nodes , skin melanoma, and pancreas.

Carcinogenesis Process

All cancers involve the malfunction of genes that control cell growth and division. The process by which cancers develop is called carcinogenesis. This process usually starts when chemicals or radiation damage DNA, the genetic structure inside cells. Viruses induce carcinogenesis by introducing new DNA sequences. Most of the time, when DNA becomes damaged the body is able to repair it. In cancer cells, however, the damaged DNA is not repaired. While normal cells with damaged DNA die, cancer cells with damaged DNA continue to multiply.

There is a long time lag between exposure to a carcinogen and the occurrence of cancer. While cellular mutations cause cancer to develop, it is not exactly clear how this happens. Carcinogenesis is a multistep process, in which as many as ten distinct mutations may have to accumulate in a cell before it becomes cancerous. The fact that so many mutations are needed for a cancer to develop indicates that cell growth is normally controlled through many sets of checks and balances.

When cells in some area of the body divide without control, these cells accumulate and form lumps. A tumor, or neoplasm, is an abnormal lump or mass of tissue that may compress, invade, and destroy normal tissue. Tumors may be benign or malignant. Cancer is a malignant neoplasm, though not all tumors are malignant. A noncancerous growth is called a benign tumor. Benign tumors do not metastasize and, with very rare exceptions, are not life threatening.

The cell cycle is regulated by a large number of cellular genes that are expressed, or exhibited, at different stages of the cycle. The genes code for, or determine, growth factors , growth-factor receptors, and proteins that control gene functions and cell survival. Damaged DNA can lead to cancer because the cell cycle is distorted by the alteration and activation of oncogenes, genes that stimulate cell growth, or by the inactivation of tumor suppressor genes, which ordinarily suppress cell growth. Activated oncogenes drive abnormal, unregulated cell proliferation and lead to tumor formation. Mutations of the tumor suppressor gene p53 are found in about 50 percent of human cancers.

In experimental animals, three stages of chemical carcinogenesis have been identified. These are: (1) initiation, where DNA is irreversibly altered; (2) promotion, which is the multiplication of altered cells; and (3) progression, which involves chromosomal changes, high growth rate, invasiveness, and potential to metastasize.

Prevention

All cancers caused by cigarette smoking and heavy use of alcohol could be prevented completely. Approximately 30 percent of all cancers worldwide are due to tobacco use. Many of the skin cancers could be prevented by protection from sunlight. Certain cancers that are related to infectious exposures, such as HBV, HPV, HIV, and Helicobacter could be prevented through behavioral changes, vaccines , or antibiotics . Research shows that about 30 to 40 percent of all cancers worldwide are due to dietary factors and lack of physical activity, including obesity, and could therefore have been prevented. By making changes in regard to diet, exercise, healthy weight maintenance, and tobacco use, the incidence of cancer around the world could be reduced by 60 to 70 percent.

The Relationship between Diet, Physical Activity, and Cancer

While the exact mechanisms by which diet is related to cancer have not been completely understood, research has shown that food plays a role in cancer prevention. For example, populations whose diet includes at least five servings of fruits and vegetables a day have lower rates of some of the most common cancers. Fruits and vegetables contain many antioxidants and phytochemicals , such as vitamins A, C, and E, and beta-carotene, which have been shown to prevent cancer. It is not completely clear, however, whether it is individual phytochemicals, or a combination of them, or the fiber in fruits and vegetables that result in reduced risk of cancer.

Studies have shown the risk of prostate cancer drops for men who eat tomato products, possibly because of the phytochemical lycopene. In addition, it has been shown that colon cancer declines among those who drink green tea, which contains antioxidants and phytochemicals, and who regularly eat soy products and foods rich in selenium, an antioxidant.

Those who eat a diet low in fat , especially animal fat, also have lower cancer rates, but again it is not clear whether it is the calories , the amount and distribution of body fat, or the likelihood that a low-fat diet is high in fiber, fruits, and vegetables that is protective against cancer. High-fiber diets are thought to reduce the risk of colon cancer because the fiber helps move food through the lower digestive tract, possibly reducing the contact of any carcinogens with the bowel lining.

Scientific evidence indicates that physical activity may reduce the risk of certain cancers. This effect may be due to the fact that physical activity is associated with the maintenance of a healthy body weight. Other mechanisms by which physical activity may help to prevent certain cancers may involve both direct and indirect effects. For colon cancer, physical activity accelerates the movement of food through the intestine, thereby reducing the length of time that the bowel lining is exposed to potential carcinogens. For breast cancer, vigorous physical activity may decrease the exposure of breast tissue to circulating estrogen , a hormone that has been implicated in breast cancer. Physical activity may also affect cancers of the colon, breast, and other sites by improving energy metabolism and reducing circulating concentrations of insulin and related growth factors.

Because of these factors, recommendations of the American Cancer Society to reduce the risk of cancer include: consumption of a mostly plant-based diet, including five or more servings of fruits and vegetables each day; consumption of whole grains in preference to processed or refined grains and sugar; limited consumption of high-fat foods, particularly from animal sources; physical activity; and limited consumption of alcohol.

Nutrition for People with Cancer

People with cancer often have increased nutritional needs. As such, it is important for them to consume a variety of foods that provide the nutrients needed to maintain health while fighting cancer. These nutrients include: protein, carbohydrates , fat, water, vitamins, and minerals . Nutrition suggestions for people with cancer often emphasize eating high-calorie, high-protein foods. Protein helps to ensure growth, repair body tissue, and maintain a healthy immune system. Therefore, people with cancer often need more protein than usual.

Great progress has been made in the fight against cancer, and cancer detection and treatments have improved significantly. However, there is a disparity in cancer death rates between developed and developing countries. Between 80 and 90 percent of cancer patients in developing countries have late-stage and often incurable cancer at the time of diagnosis.

A growing body of evidence shows that simple changes in diet and lifestyle can help prevent many cancers. Further research into the exact mechanisms by which certain diets may help prevent cancer is ongoing.

see also Antioxidants; Functional Foods; Phytochemicals.

Gita C. Gidwani

Bibliography

American Institute for Cancer Research (1997). Food, Nutrition, and the Prevention of Cancer: A Global Perspective. Washington, DC: Author.

Cooper, Geoffrey M. (1992). Elements of Human Cancer. Boston: Jones and Bartlett.

Tortora, Gerald J., and Grabowski, Sandra Reynolds (2003). Principles of Anatomy and Physiology, 10th edition. New York: Wiley.

Internet Resources

American Cancer Society. "Cancer Facts and Figures, 2002." Available from <http://www.cancer.org/downloads>

National Cancer Institute (2000). "Cancer Facts: Questions and Answers About Cancer." Available from <http://www.nci.nih.gov>

Cancer

Cancer develops when cells in the body begin to grow out of control. Normal cells grow, divide, and die. But cancer cells, instead of dying, continue to

grow and form new abnormal cells. Cancer cells often travel to other body parts where they grow and replace normal tissue. This process, called metastasis, occurs as the cancer cells are transported by the bloodstream or lymph vessels. Cancer cells develop because of damage to DNA. DNA carries the genetic information of every cell and directs all its activities. When DNA becomes damaged, the body is able to repair it. But in cancer cells, the damage is not repaired.

Some anomalies that increase the risk of cancer are present at birth in the genes of all cells in the body, including reproductive cells. These can be passed from parent to child. This is known as inherited susceptibility and is an uncommon cause of cancer. Most cancers result from genetic changes that occur over decades within the cells of a particular organ. These changes can usually be traced to an interaction of genetics and the environment, including behavior and lifestyle. Other factors that influence cancer risk are age, race, gender, preexisting disease, and nutritional impairment.

Environmental Factors

The term "environment" includes air, water, and soil, as well as substances and conditions in the home and workplace. It also includes:

• Diet
• Use of tobacco, alcohol, or drugs
• Exposure to chemicals
• Exposure to ultraviolet (UV) light from the sun and in tanning parlors and other forms of radiation

Only recently have scientists proved the existence of an interaction between environmental toxins and one's genetic makeup. Researchers hope that when people are knowledgeable about inherited susceptibility, they will be motivated to avoid carcinogens that increase their risk. For example, scientists at the State University of New York at Buffalo report evidence that a genetic variation (mutation) in a gene which helps detoxify carcinogens may put smokers with this mutation at increased risk for breast cancer.

Overexposure to UV radiation from the sun and cigarette smoking pose the greatest known risks of developing cancer. Other factors contribute much less significantly to cancer development. The approximate lifetime risk of developing cancer from known causes is listed in descending order of risk in the bar graph. Note that the risk from exposure to chemicals at hazardous waste sites can vary widely, depending on the chemical, and the length and type of exposure. For comparison, consider the fact that the lifetime risk of death from a fall is 1 in 270, according to the National Safety Council. The lifetime risk of any given American dying as an automobile passenger or a motorcycle rider are 1 in 244 and 1 in 1,536 respectively.

Categories of Carcinogenicity

Substances or agents that cause cancer are called carcinogens . The more likely something is to cause cancer, the more carcinogenic it is. Cigarette smoke is more carcinogenic than chlorinated community drinking water.

The U.S. Environmental Protection Agency (EPA) classifies carcinogenicity into five categories. A category A substance is known to cause cancer in humans, generally based on epidemiological (large population) data showing sufficient evidence to support a causal association between exposure to the substance and cancer. Category A carcinogens include asbestos, benzene, radon, and coal gasification. Category B includes "probable" human carcinogens known to cause cancer in animals but not yet definitively shown to cause cancer in humans. Category B carcinogens include chloroform, carbon tetrachloride, gasoline, and progestins. Category C includes "possible" human carcinogens for which the data show "limited evidence" of carcinogenicity in the absence of human data. Chemicals for which the data are incomplete, inadequate, or ambiguous are "not classifiable" and reside in category D. Those in category E are "probably not carcinogenic."

Determining carcinogenicity can be a harrowing and lengthy process. For example, the debate over possible risks posed by electromagnetic fields (EMF) has been raging for decades. Magnetic fields originate from everything with an electrical current. Elevated field levels can occur in homes close to power lines, or occasionally from improper household wiring. A form of EMF called "extremely low frequency (ELF) electric and magnetic fields" recently was classified as "possibly carcinogenic" by the International Agency for Research on Cancer (IARC).

Concerns about EMF from power lines began to mount in the 1970s, when epidemiological studies first showed a possible link to childhood cancer. But the research has produced inconsistent and conflicting findings, leading the World Health Organization (WHO) in 2002 to launch a more complete series of follow-up studies.

Military personnel in proximity to radio frequency (RF) emitted by radar equipment may have an increased risk of brain cancer, according to a small published Israeli study. But when it comes to RF, cellular phones have been receiving the bulk of attention from the media and in lawsuits claiming that cell phone use resulted in plaintiffs' brain tumors. While researchers have shown that the use of these handheld devices increases a driver's risk of experiencing a traffic accident, the brain tumor connection remains unproved.

When a person develops a malignancy, it can be very difficult to attribute a particular cause or source. Though smoking underlies the bulk of environment-induced lung disease, there are other contributors or possible contributors in human surroundings. Some evidence suggests that air pollutants produced by the burning of fossil fuels play a role in causing lung cancer among city dwellers. A high level of radon in the home—such as exists in parts of the Midwest and northeast—is a cancer risk factor, especially for smokers. Radon is a heavy, radioactive gaseous element formed by the natural decay or disintegration of radium in the earth's crust. Other environmental pollutants that may play roles in cancer include airborne arsenic and microscopic asbestos fibers inhaled into the lungs.

Radon is not alone in adding to the lethality of cigarette smoking. Asbestos exposure and smoking also multiply each other's lethality (a "synergistic" effect). On an individual basis, both smoking and asbestos exposure can cause lung cancer, but taken together, they multiply the risk of lung cancer significantly. Studies in the science of epidemiology confirm that the combination of smoking and asbestos exposure creates a risk of cancer much higher than just adding together their separate risks. Evidence suggests that asbestos-exposed workers who quit smoking can reduce their risk of developing lung cancer by as much as 50 percent within five years of quitting.

Cancer Clusters

The study of disease clusters is one method scientists use to study the public health implications of carcinogens. A cancer cluster is defined as a greater-than-expected number of cancer cases that occurs within a group of people in a geographic area over a specific period of time. Studies of suspected cancer clusters usually focus on heredity and environment. Such clusters may be suspected when people report that several family members, friends, neighbors, or coworkers have been diagnosed with the same or related cancer(s).

In the early 1980s a leukemia cluster was identified in the Massachusetts town of Woburn. In a case that was the subject of A Civil Action, later made into a major motion picture, three companies were accused of contaminating drinking water and causing illnesses. The case went to trial in Anne Anderson, et al. v. W.R. Grace & Co., et al. Six families alleged that chemicals dumped by the defendants caused leukemia in members of those families. Two closed municipal water wells—which were the focus of the families' case—were found to be contaminated with EPA-listed hazardous substances, including trichloroethylene (TCE). Although the U.S. Department of Health and Human Services (HHS) lists TCE as "reasonably anticipated to be a human carcinogen," IARC has determined that trichloroethylene cannot currently be classified as such.

In any case, this action became a poster trial for the difficulty of linking certain events to a cluster of individual illnesses. The incredibly complex case involved thirty-three plaintiffs, two defendants, a mountain of conflicting geological and medical testimony, and multiple claims including negligence, nuisance, and emotional distress. A direct and incontrovertible connection between the pollution caused by W.R. Grace and the cancer cluster was never confirmed.

The prospect of a larger cancer cluster was investigated in New York State. The Breast Cancer and the Environment on Long Island Study was carried out in response to anecdotal reports that environmental toxins elevated breast cancer rates among women in the region. Chief among the suspects were polycyclic aromatic hydrocarbons (PAH), which are caused by incomplete combustion of various chemicals including diesel fuel and cigarette smoke, and organochlorine compounds, which are found in many pesticides. In August 2002 scientists reported that organochlorine compounds were not associated with the elevated rates of breast cancer on Long Island. However, the same investigators did suggest it was possible that risk in some individuals may be associated with organochlorine exposures because of individual differences in metabolism and the ability of one's body to repair DNA damage.

The researchers also found that PAHs were associated with a modest 50 percent increased risk for breast cancer in susceptible women exposed to high levels of the compounds. But for the population of women as a whole, no specific environmental factor could be tied to the incidence of breast cancer. Some have complained that the study failed to take into account the possible effects of leaks from a nearby nuclear reactor, and there have been public accusations that the study avoided the so-called "nuke connection" for political and financial reasons.

The thousands of individuals who were in and around the World Trade Center in lower Manhattan on and immediately after September 11, 2001, may constitute a cluster of future disease. Public safety personnel, rescue workers, and local residents were exposed to a lingering pall of dust and debris following the collapse of the twin towers and other buildings. Super-heated and aerosolized building materials created an incalculable number of toxic compounds. The full effects on the health of those exposed may not be known for decades.

In conclusion, the interplay between our environment and cancer is complex and not yet fully understood. It is increasingly clear that the unborn and very young children are particularly susceptible to environmental toxins such as endocrine-disrupting herbicides and insecticides. Adult cancer risk can be greatly reduced by avoiding tobacco products and limiting sun exposure. Known carcinogens often encountered in workplaces and homes include pesticides, asbestos, arsenic, uranium, and certain petroleum products.

see also Asbestos; Health, Human; PCBs (Polychlorinated Biphenyls); Radon; Risk.

Bibliography

Fackelmann, Kathleen. (1995). "Variations on a Theme: Interplay of Genes and Environment Elevates Cancer Risk." Science News 147(187):280.

"Extremely Low Frequency Electromagnetic Fields—W.H.O. Classifies The Cancer Risk (Update)." (2002). Journal of Environmental Health 65(5):47.

Munshi, A., and Jalali, R. (2002). "Cellular Phones and Their Hazards: The Current Evidence." National Medical Journal of India 15(5):275–277.

Richter, E.D.; Berman, T.; and Levy, O. (2002). "Brain Cancer with Induction Periods of Less than 10 Years in Young Military Radar Workers." Archives of Environmental Health 57(4):270–272.

Internet Resources

Asbestos Network Web site. Available from http://www.asbestosnetwork.com.

Harvard Medical School Web site. Available from http://www.intelihealth.com.

International Agency for Research on Cancer (IARC) Web site. Available from http://www.monographs.iarc.fr/.Int.

National Institutes of Health and National Cancer Institute Web site. Available from http://www.cis.nci.nih.gov.

U.S. Centers for Disease Control and Prevention Web site. Available from http://www.cdc.gov/nceh.

U.S. Environmental Protection Agency Web site. Available from http://www.epa.gov.

Bruce K. Dixon

Cancer

Cancer is a number of related diseases that are characterized by the uncontrolled proliferation and disorganized growth of cells. Tumor cells invade and destroy normal tissues and may spread throughout the body via the circulatory systems.

A Genetic Disease

Cancer is the result of changes in the genetic material of a cell that cause the cell to gradually lose the ability to grow in a regulated fashion. These changes can be brought about by contact with harmful environmental agents or by inheritance of genes leading to a genetic predisposition .

Cancer risk increases with age, as the probability of accumulating mutations in the DNA increases with time. Environmental factors include lifestyle (e.g., smoking), diet (e.g., saturated fats from red meat), and exposure to certain chemicals (e.g., asbestos, benzopyrenes), ionizing radiation (e.g., X-rays, radon gas), ultraviolet radiation (e.g., sun, tanning beds), and certain viruses (e.g., human papillomavirus, Epstein-Barr virus). Heredity also plays a role in oncogenesis , as mutations in certain genes increase the probability of developing certain types of cancer. For instance, women who inherit a mutated copy of the BRCA1 or BRCA2 gene have a greatly increased probability of developing breast cancer at a young age.

Classification of Cancer Types

The term "cancer" is general, in that it represents a large group of related diseases that arise from neoplasms . A neoplasm is classified by the type of tissue in which it arises and the stage to which it has progressed. Neoplasms are also called tumors. Not all tumors are cancerous. A tumor that grows in one place and does not invade surrounding tissue is called benign. In contrast, invasive tumors are called malignant. These are cancerous.

Benign or Malignant Tumor

Whether a tumor is benign or malignant determines how potentially life-threatening it is. Benign tumors are usually harmless, although their location may be serious (if surgery to remove the tumor would carry significant risk). These tumors are not considered cancerous, are relatively slow-growing, and usually are encased within a fibrous capsule.

Malignant tumors (cancers) have great potential to spread, or metastasize, to other sites in the body. These tumors are fast-growing and aggressive, and they invade neighboring healthy tissue. They therefore are considered life threatening.

Type of Tissue

The body consists of many different organs, which in turn are composed of several different types of tissues. There are three major categories of tissue-related tumor types: carcinoma, sarcoma, and leukemia/lymphoma. There are also other specialized tumor categories, such as those of the central nervous system (e.g., brain tumors).

Carcinoma.

This is the largest category, containing about 90 percent of all cancers, and it consists of neoplasms derived from epithelial cells. Epithelial cells make up the outer layers of the skin. They also line the inner structures of organs such as the lungs, intestines and testes, as well as complex tissue such as the breast.

Sarcoma.

These are solid tumors derived from all connective tissues except the bloodforming tissues (these are the leukemias and lymphomas). These tumors account for about 2 percent of all cancers. They occur in such tissues as muscle, bone, and cartilage.

Leukemia and Lymphoma.

This group contains about 8 percent of all cancers, including blood cancers that originate from the marrow (leukemias) and from the lymphatic system (lymphomas). This group also includes other nonsolid tumors of the bone marrow and lymphatic system, such as myeloma, which affects plasma cells—a type of white blood cell found in the marrow and in other tissues.

Type of Cell

Classifying a tumor by the type of cell from which it is derived is slightly more complex than classifying it by the type of tissue, since there are so many cell types. The main cell types include adenomatous cells (which are ductal or glandular cells), basal cells (found at the base of the skin), myeloid blood cells (granulocytes, monocytes, and platelets), lymphoid cells (lymphocytes or macrophages), and squamous cells (flat cells). Therefore it is possible for a cancer classified by its site of origin to be broken up into one of several cell types. For example, a skin cancer could be either a squamous cell carcinoma, a basal cell carcinoma, or a melanoma (from a pigment-producing cell).

Site of Origin

Solid tumors are firm masses that develop from a neoplasm's originating organ, such as the brain, esophagus, kidney, liver, lung, ovary, pancreas, prostate, or testis. Tumors of the blood-forming tissues and lymphatic systems are not solid and tend to remain free and circulating even when malignant. Some of the common forms of cancer are listed in the table above.

Cancer Progression

There two main steps in cancer progression: the initial growth of the cancer and the subsequent spread via metastasis . Solid tumors are subject to the physiological constraints of biological systems: Without nutrients and oxygen, they will die. Therefore a solid tumor is initially limited in size to no larger than 1 to 2 millimeters in diameter (about the size of a small pea).

For a tumor to become aggressive, it needs to be able to nourish the cells at the center of its mass that are too far away from blood vessels. This is achieved by angiogenesis . Through mutation, a few cancer cells may gain the ability to produce angiogenic growth factors. These growth factors are proteins that are released by the tumor into nearby tissues, where they stimulate new blood vessels to grow into the tumor. This allows the tumor to rapidly expand in mass and invade surrounding tissue. It also provides a route for the cancer cells to escape into the new blood vessels and circulate throughout the body, where they can lodge in other organs forming metastases.

The most common way for a cancer to metastasize is through the lymphatic system. The lymphatic system is a network of channels throughout the body that carry a tissue fluid called lymph.

When a primary neoplasm metastasizes to another location, its cell type does not change. If leukemia metastasizes to the liver and develops a tumor, the tumor will display the characteristics of the leukemia, not those of a liver cancer. In some cases this can help physicians determine the original site of a tumor.

Genes Altered in Tumors

Although each cell in the body maintains itself and carries out its specific function, it is part of a large colony of collaborating cells that constitute the whole organism. A cell communicates with its surrounding cells by releasing chemical messages, in a process called signal transduction. These messages bind to specific receptor proteins on the surface of the surrounding cells. The gene expression of these cells is changed as a result of the messages.

A hyperplastic cell or a cancerous cell will stimulate neighboring cells to grow by secreting growth factors. Several types of genes can be mutated in tumor cells: oncogenes, tumor suppressor genes, DNA repair genes, and genes involved in cell mortality.

Oncogenes.

These genes are involved in signal transduction, and some are involved in the various phases of the cell cycle. Mutations in cell-cycle regulation or signal transduction can "push" the cell into dividing rapidly and without regard to its surroundings. Over 100 oncogenes have been identified so far. They include genes such as ABL1 (Abelson murine strain leukemia viral homolog) and EGFR (Epidermal Growth Factor Receptor).

Tumor Suppressor Genes.

These genes inhibit cell division, working in a manner opposite to that of the oncogenes. Surrounding cells secrete growth-inhibitory signals that help prevent proliferation. These growth-inhibitory signals work in conjunction with tumor suppressor genes. If a tumor suppressor gene is mutated, proliferating cells can ignore these inhibitory messages. This group includes the genes p53, BRCA1, and BRCA2.

DNA Repair Genes.

These are the genes that provide the cell with the ability to sense and correct damage to the DNA. Damage to the DNA can be caused by radiation, chemicals, ultraviolet light, or errors in transcription. If these errors are not corrected, they accumulate in the genome and can quickly increase the chance that a cell will become cancerous. Repair genes include those in the DNA-ligase and excision-repair gene families.

Genes Involved in Cell Mortality.

A normal cell can only undergo about forty divisions, after which it dies or enters senescence . If a tumor had this limitation it would be very limited in its size, as it would reach its forty divisions relatively quickly. This process is controlled by the enzyme telomerase, which maintains the telomeres (repetitive DNA sequences at the ends of chromosomes that shorten after each round of DNA replication, until they reach a length that causes the cell to die) by not allowing them to shorten. Some cancer cells become immortal as a result of mutations in the telomerase gene, causing the telomeres to be extended indefinitely, allowing the cell to continue dividing without limit. Other mutations affect the process of apoptosis .

Cancer does not usually arise by a single event. Instead, two or more "hits" are needed to convert a well-regulated cell to a cancer cell. This is the case because each cell contains two copies of each gene, one inherited from each parent. Most cancer-causing mutations cause a loss of function in the mutated gene. Often, having only one functional copy is enough to prevent disease. Thus, two mutations are needed.

This can be illustrated by looking at retinoblastoma, a common cancer of the retina. The affected gene (called the retinoblastoma gene) is a tumor suppressor. Spontaneous mutations are rare, but since there are many millions of cells in the retina, several will develop the appropriate gene mutation over the course of a lifetime. It would be very unlikely, though, for a single cell to develop two spontaneous mutations (at least in the absence of prolonged exposure to carcinogens), and thus spontaneous retinoblastoma is very rare.

If, however, a person inherits one copy of an already-mutated gene from one parent, every cell in the eye starts life with one "hit." The chances are very high that several cells will suffer another hit sometime during their life, and so the chances are very high that the person will develop retinoblastoma. Since inheriting a single copy of the mutated gene is so likely to lead to the disease, the gene is said to show a dominant inheritance pattern.

Future Directions in Diagnosis and Treatment

The increased knowledge of cancer at the biochemical and genetic level has led to many advances toward better diagnosis and treatment of cancer, including the design of more specific drugs that are less toxic to normal tissue. This includes the use of antisense molecules, which are nucleic acid sequences that are complementary to the mRNA of a target gene. As the two sequences are complementary, they anneal and thus the mRNA is blocked from being translated into a protein, resulting in less of that particular protein being produced (such as growth factor receptors). Drugs specific in blocking angiogenesis are able to control the growth and spread of tumors, especially when used in combination with other treatments.

see also Ames Test; Antisense Nucleotides; Apoptosis; Breast Cancer; Carcinogens; Cell Cycle; Colon Cancer; DNA Repair; Mutagen; Mutation; Oncogenes; Signal Transduction; Telomere; Tumor Suppressor Genes.

Giles Watts

Bibliography

Greider, C. W., and E. H. Blackburn. "Telomeres, Telomerase and Cancer." Scientific American 274 (1996): 80-85.

Kiberstis, Paula, and Jean Marx. "The Unstable Path to Cancer." Science 297, no. 5581 (2002): 543.

Lenherd, Raymond E., et al. Clinical Oncology. Atlanta, GA: American Cancer Society, 2001.

Rosenberg, S. A., and B. M. John. The Transformed Cell: Unlocking the Mysteries of Cancer. New York: Putnam, 1992.

Weinberg, R. A. Racing to the Beginning of the Road: The Search for the Origin of Cancer. New York: Putnam, 1998.

Weinberg, R. A. One Renegade Cell: How Cancer Begins. New York: Basic Books, 1999.

Cancer

Research and Treatment

In 1993 1.1 million new cases of cancer were reported in the United States. Cancer of the lung ranked first in number of occurrences, followed by cancer of the colon. Researchers found that a faulty MSH2 gene, detectable by a blood test, predisposed one in two hundred people to the development of colon cancer. Another blood test, the PSA (prostate specific antigen), showed an elevation in the presence of prostate cancer and became an effective screening technique for the early stages of the disease. Basic research on multiple fronts sought new ways to treat or prevent cancer. Dr. Judah Folkman, director of the Surgical Research Laboratories, Children's Hospital of Boston, discovered two drugs, endostatin and angiostatin, which could cure cancer in mice by altering new blood vessel growth. Although there was no evidence that this treatment would work in humans, the price of stock in his biotech firm increased from $12 to $85 a share. Folkman once quipped, "As long as there is an unconquered disease, we have an obligation to pursue research… [For now], if you have cancer and you are a mouse, we can take good care of you." On a less high-tech level, phytochemicals (plant-derived nutrients) and other naturally occurring compounds were promoted as cancer preventives and widely marketed as food supplements.

Breast Cancer

Women became more politically active and vocal in asserting their demands for research into breast cancer and other diseases that affected them. In 1990 there were 43,700 deaths from breast cancer, while annual government research funding was $77 million; the same year 23,739 people died from AIDS, whereas funding for research into this disease was $1.1 billion. By 1997 research funding for breast cancer increased to $340 million per year (compared to $220 million for AIDS and $125 million for lung cancer). Despite the paucity of funding, new techniques for diagnosis were developed, such as the stereotactic biopsy, where the suspicious mass is marked with a wire and the nonsurgical, needle biopsy is carried out under digitalized X-ray control. Clinical trials with medications such as B-Oval (a birth control pill) and tamoxifen (an estrogen inhibitor) were undertaken; the latter seemed to decrease the incidence of breast cancer in high-risk women. A Mayo Clinic study showed that prophylactic mastectomy (the removal of a breast with no known disease) could reduce the risk of developing breast cancer by 90 percent. In the area of early detection, a debate raged over recommendations regarding mammography for younger women. The National Cancer Institute reversed its original recommendation and backed mammography for women beginning at age forty. This change was significant since insurance companies might have balked at paying for the screening study if the first recommendation had remained in effect Politicians endorsed the new shift, but changing a medical policy because of public pressure rather than new data troubled some scientists.

GULF WAR SYNDROME

About 697,000 men and women of the U.S. military served in the Persian Gulf War during 1990 and 1991. Some returned home with various illnesses such as rash, asthma, short-term memory loss, fatigue, muscle aches and pains, and weakness. This grouping of diverse symptoms affecting returning veterans became known as the Gulf War syndrome. In spite of receiving medical discharges, some veterans were denied full disability pay. The military and the Veterans Affairs Department initially dismissed the complaints as not being related to service in the Persian Gulf.

Spouses of some veterans came down with some of the symptoms as well, and some of the pregnancies following service in the Gulf resulted in premature births and an elevated incidence of birth defects and neonatal illnesses. The potential causes of the syndrome are as varied as its symptoms. Soldiers breathed smoke from burning waste clumps and oil wells and encountered a variety of paints, solvents, and pesticides. Some veterans believe they were exposed to chemical or germ warfare agents that were dispersed into the air after the allied bombing of Iraqi storage facilities. The Pentagon acknowledged that it had detected minute traces of sarin (a nerve agent) and mustard gas in the desert. Another potential source of the problem may have been medications administered to the soldiers, such as pyridostigmine bromide, a drug given to four hundred thousand soldiers to protect them against chemical weapons.

Researchers at Duke University and the University of Texas linked the veterans' problems to chemicals used to protect them from insects and nerve gas. The study showed that even in small amounts, cholinesterase inhibitors used in combinations can cause an illness resembling Gulf War syndrome. Animals treated with only one of the drugs in question did not develop illnesses, but those receiving both the anti-nerve-gas pill and the insect repellents did exhibit symptoms.

In 1999 a report prepared for the Defense Department "could not rule out" the drug pyridostigmine bromide (PB) as a possible cause of the syndrome. The Defense Department has spent $100 million on Gulf War Health Research since 1994, and had $17 million worth of studies on PB underway. While no definitive answer was determined as to the etiology' of the Gulf War illness, the Department of Veterans Affairs and the Department of Defense now recognize that the syndrome is a real entity.

Sources:

David Brown, "'Gulf War Syndrome' Study Looks at Nerve Gas Protection," The Washington Post. 19 October 1999.

Geoffrey Cowley. "Coming Home to Pain: Why Are So Many Gulf War Veterans So Siokr?" Newsweek, 121 (28 June 1993): 58-59.

Cowley. "Tracking the Second Storm." Newsweek, 123 (16 May 1994): 56-57. Cowley and Mary Hager. "Poisoned in the Gulf?: New Clues to the Veterms' Mysterious Illness," Newsweek, 127 (29 April 1996): 74.

Politics and Smoking

Public pressure, along with concern by state governments about medical-care costs, led to an attack on the cigarette industry. As Dr. Thomas D. MacKenzie argued in a New England Journal of Medicine (1994) article, "cigarettes remain the only consumer product sold legally in the U.S. that is unequivocally carcinogenic when used as directed." Dr. William L. Roper, director of the Centers for Disease Control and Prevention (CDC), noted in 1991 that it can take up to twenty years for cancer caused by smoking to develop. In 1993 the University of California and the CDC calculated that the cost of tobacco-related illness was at least $50 billion per year. Secretary of the Department of Health and Human Services (HHS), Dr. Louis W. Sullivan, denounced the tobacco industry for test-marketing cigarettes aimed at African Americans, and the R. J. Reynolds Company canceled the introduction of a new brand aimed specifically at blacks. Sullivan also criticized tobacco industry sponsorship of athletic events, as well as ads directed toward women, minorities, and the young. "Joe Camel" ads, featuring a suave cartoon camel, came under the strongest attacks since they seemed to effectively target children; the macho image of the "Marlboro Man" was also targeted. Americans were not the only people vulnerable to these illnesses and advertisements. In order to offset domestic declines in cigarette consumption the U.S. tobacco companies aggressively marketed their product abroad.

Side Effects

Secondhand smoke was implicated in multiple health problems. The Environmental Protection Agency (EPA) reported that such smoke caused 3,000 lung cancer deaths, contributed to 105,000 to 300,000 respiratory infections in infants, triggered 8,000 to 26,000 new cases of asthma, and exacerbated symptoms in 400,000 to 1 million asthmatic children per year. Based on this evidence, multiple lawsuits were filed against cigarette manufacturers. They had faced suits before but were uniformly victorious in the courtrooms, utilizing the defense that they produced a legal product that people could use or not as they wished, and if they chose to use it, they were freely accepting any risks involved.

Tobacco Under Attack

During the new legal siege, executives of the cigarette-producing companies were forced to give testimony. Each new suit seemed to introduce new information about what the tobacco company executives knew concerning the health hazards of the product, such as whether it caused cancer and was addictive, as well as about alleged manipulation of cigarette ingredients to increase nicotine levels. Evidence mounted that the industry targeted teenagers in order to maintain a steady supply of customers. After contentious argument within Congress and between Congress and President Bill Clinton, a deal was finally reached. The industry agreed to a settlement of close to $400 billion, in part to stop the onslaught of suits in virtually every state. Data for 1999 showed a 7 to 9 percent decrease in cigarette consumption, which may be attributed to the price jump of 45 cents per pack. Many of the states chose to use the money as general revenue rather than designating it for antismoking or education programs or for health programs. According to the National Conference of State Legislatures, only 8 percent of the $206 billion that the tobacco companies were to pay the states under the settlement went to antismoking efforts.

Sources:

Carl E. Bartecchi, Thomas D. MacKenzie, and Robert W. Schrier, "The Global Tobacco Epidemic," Scientific American, 272 (May 1995): 44-51.

Melinda Beck and Lucille Beachy, "The Politics of Breast Cancer," Newsweek, 116 (10 December 1990): 62-64.

Sharon Begley, "Beyond Vitamins," Newsweek, 123 (25 April 1994): 45-48.

Begley, "The Mammogram War," Newsweek, 129 (24 February 1997): 54-57.

Begley, "New Hope for Women at Risk," Newsweek, 131 (20 April 1998): 68-70.

Begley and Claudia Kalb, "One Man's Quest to Cure Cancer," Newsweek, 131 (18 May 1998): 55.

Geoffrey Cowley, "Are Supplements Still Worth Taking," Newsweek, 123 (25 April 1994): 47.

Cowley, "I'd Toddle a Mile for a Camel" Newsweek, 118 (23 December 1991): 70.

Cowley, "A Needle Instead of a Knife" Newsweek, 119 (13 April 1992): 62.

Cowley, "Poison at Home and at Work," Newsweek, 119 (29 June 1992): 55.

"A Grim Legacy for Longtime Smokers," Newsweek, 118 (11 February 1991): 58.

Claudia Kalb, "Hype, Hope, Cancer," Newsweek, 132 (28 December 1998): 73.

Jeffrey Kluger, "Mammogram Two-Step," Time, 149 (7 April 1997): 67.

Richard Lacayo, "Smoke Gets in Your Aye," Time, 151 (26 January 1998): 50.

Charles Leerhsen, "Searching for a Better Pill: Can It Deter Breast Cancer?" Newsweek, 117 (8 April 1991): 56.

John Leland, "A Whiff of Smoking Guns," Newsweek, 126 (7 August 1995): 56-57.

Thomas D. MacKenzie, Carl E. Bartecchi, and Robert W. Schrier, "The Human Costs of Tobacco Use (Second of Two Parts)," New England Journal of Medicine, 330 (7 April 1994): 975-980.

Tom Morganthau, "Sullivan: Bush's Aide Makes Waves," Newsweek, 115 (5 March 1990): 19.

"A Radical Solution," Newsweek, 133 (25 January 1999): 68.

"Tobacco Wars, Still," Washington Post, 29 December 1999.

Cancer

Cancer is the uncontrolled growth of cells. This abnormal growth is the result of mutations in the genetic material of the cells, either spontaneous or brought on by environmental factors such as ultraviolet radiation or asbestos. This growth leads to a collection of mutated cells called a tumor. The tumor can be benign, meaning that it is comparatively harmless and restricted to one type of tissue. Alternately, it can be malignant, which means it can grow into surrounding tissue or migrate to different parts of the body. When a malignant tumor spreads to other tissues, this is known as metastasis.

Cell replication

Normally, animal cells grow with a variety of checkpoints. For example, when a person cuts her finger, skin cells will divide and grow to fill the opening, but they will stop growing once the cut is closed. The body has a number of mechanisms to prevent unchecked cell growth, and in order to become cancerous, abnormal cells must defeat several of them. Some of these mechanisms determine division rates; others manage DNA repair. Like any other controls in the body, these can go awry when a mistake arises in the DNA encoding them.

Excessive cell division.

Suppose, again, that a person gets cut. First, skin cells must decide when it is time to divide and when it is time to rest. Often cells will receive signals from outside their membranes instructing them what to do, and the signals must pass down a cascade of messengers inside the cell for them to be conveyed. Each step along the cascade, then, can be a control point: a surface molecule on a skin cell is told that it must divide to heal a cut, and the surface molecule sends a signal to a protein inside the cell, which sends the signal to a different protein, and so on, all the way to the nucleus, which then initiates DNA replication and cell growth. At each step, it is possible that a mistake might start or halt the cell replication process. For example, overexpression of ras, an intracellular messenger that resides in the pathway between the surface and the nucleus, can lead to excessive cell division.

Viruses and cancer.

There are a number of ways that a protein such as ras can be overexpressed, including the involvement of a virus or a genetic mutation. Certain viruses are associated with cancers: for example, sexually transmitted human papilloma virus has been known to increase rates of cervical cancer. Out of all cancers, 10 to 15 percent are thought to be virus-related. Alternately, the genetic mistake might be spontaneous in one of three ways. A gene encoding the protein could be accidentally copied more than once, and, as a result, each copy would churn out the protein when activated. The gene could be misplaced and put near a region of DNA that encourages protein expression. Lastly, a mutation inside the gene might make it unusually active or resistant to later degradation. When such errors initiate uncontrolled cell growth, the gene involved is called an onco-gene (onco is Greek for "tumor"). Before the mutation occurs, the gene may be called a proto-oncogene. Proto-oncogenes usually have the important function of controlling cell-cycle function, as is the case with ras, or may be involved in keeping the cell alive during times of stress, as in the case of Bcl-2, a molecule that prevents stressed or damaged cells from committing apoptosis (cell suicide). Certain viruses can cause these mutations and make oncogenes out of the protoncogenes.

How Cells Curb Their Own Growth

Mutations in cell-cycle control genes can obviously be a problem for an individual, so there are mechanisms in place to prevent this from happening. As mutations can happen during DNA replication, DNA copying is a tightly controlled process. Additionally, there are genes that have the task of DNA repair and mutation surveillance. One such gene is p53. If there is genetic damage, p53 will halt the cell cycle, may initiate DNA repair mechanisms, and may activate cell suicide if repair is not feasible. P53 and other genes that conduct DNA repair and damage surveillance are called "tumor suppressor genes."

Apoptosis.

Apoptosis is a way for damaged cells to prevent themselves from causing more problems. Once apoptosis is initiated, the cell cleaves its own DNA and falls apart in a tightly regulated fashion. The dying cell will pinch off into small pockets of membrane and organelles , known as apoptotic bodies, in order to prevent toxic cytosolic compounds from being released. Then the apoptotic bodies will be swept up and cleared from the area by macrophages or other cells.

"Slipperiness."

Aside from cell-cycle control and tumor suppressor genes, there are other means by which cells curb their own growth. For example, if one grows ordinary skin cells on a plate with growth media, the cells will grow until a bed covers the entire plate. But the cells will not grow beyond that; nor will they grow on top of one another. This is why a cut on one's finger will not grow into a huge lump after it closes. Normal cells will also adhere tightly to one another by secreting proteins that stick to other cell surfaces, whereas many cancer cells do not. Medical doctors use this lack of adhesion, this slipperiness, as one way of distinguishing cancerous tumors from other kinds of lumps.

Telomerases.

Another common mutation seen in cancers is the activation of telomerases. When DNA divides, the replication machinery moves down the nucleotide chain until the very end. It is unable to copy the very end of the molecule (the telomere), however, so with each successive round of replication, the DNA chain gets shorter. In mammals, the telomeres contain repetitive DNA sequences that encode no protein; the idea is that these useless nucleotides can be discarded as cells divide. As the telomeres get shorter, though, the cell will eventually start deleting useful DNA. Some scientists think this is a reason animals grow old: The more cells divide, the greater the likelihood that certain genes will be eliminated and that the new cells will be dysfunctional.

Cancer Cells

Cancer cells, on the other hand, have no such problem. They usually express telomerases, which are enzymes designed to prevent the elimination of the telomeres during cell division. Cancer cells can therefore divide many times and not delete any genetic information crucial to their survival.

Cells require more than one mutation to become cancerous. Mutations in cell-cycle control and tumor suppressor genes are usually required for a tumor to be considered a full-fledged cancer. While many of the tumor suppressor genes are dominant traits (requiring only one allelic deletion to deactivate), many proto-oncogenes are recessive , meaning that both alleles must be destroyed in order for the cells to grow improperly. Such a combination of mutations in a single cell is unlikely, which is why some scientists think that cancers do not begin to show in humans until late in life, when repeated cell division has had a chance to accumulate a number of mistakes in the DNA.

After p53 or other genes that screen DNA get deleted, the cells begin to spin out of control genetically and produce many different kinds of mutations. Like most mutations, the majority of these will simply kill off the cells possessing them. But as tumor cell division is unchecked, other cells will quickly replace them. As the tumor grows and accumulates more mutations, it may gain the ability to grow in different types of tissue.

Cancers may acquire a number of traits useful for their own growth. For example, certain tumors are angiogenic, meaning they draw blood vessels toward themselves to feed the growing tumor. The malignant cells do this by secreting certain hormones necessary for vessel formation. These new vessels also provide conduits for cancer cells to spread throughout the body. In the early twenty-first century, researchers also found that some tumor cells can create new lymphatic vessels, a process called lymphangio-genesis. These newly generated vessels may make it easier for the cancer to spread itself to other parts of the body.

Cancer Treatment

As one might predict, cancer treatment primarily seeks to stop the division of the cells. One method is radiation, which disrupts DNA replication entirely. Other pharmacological means seek to do the same. As cancers are usually the only collection of rapidly dividing cells in the body, halting replication can slow them down, although such treatments can impede healing or immune system function.

More recently, researchers have been using compounds designed to prevent angiogenesis to curb tumor growth. In the early twenty-first century, the National Cancer Institute was conducting clinical trials of anti-angiogenic compounds in a variety of cancers, including stomach, breast, prostate, lung, brain, and ovary, and in some leukemias and lymphomas.

Certain cancers produce tumor antigens, proteins recognizable by the body as hailing from a cancer. Prostate cancer, for example, generates tumor antigens specific enough to be used as a diagnostic tool in patients. Thus, it is theoretically possible to create a prostate cancer vaccine by teaching the body to recognize these antigens before cancer ever arrives and to fight off malignant cells, just as antivirus vaccines fight off virally infected cells. By the beginning of the twenty-first century, however, researchers had found vaccines to be of little use in specifically stimulating the body's immune system to reject tumors.

Cancers, ordinary cells gone wrong, defy normal biological conventions of regulation and homeostasis . As they can quickly reproduce and replace lost daughter cells, they are ripe for rapid mutation and evolution within the body. A variety of treatments exist, but cancers vary widely in origin and nature, as there are different regulatory mechanisms that control different cell types. A more detailed understanding of cell-cycle regulation and mutation surveillance may yet unlock the secrets to curing the disease.

see also Cells.

Ian Quigley

Bibliography

Scientific American. Special Topic Issue: "What You Need to Know about Cancer." September 1996.

Internet Resources

Cancernet. National Cancer Institute. <http://cancernet.nci.nih.gov/>.

HELA CELLS

Although Henrietta Lacks died of cancer in 1951, little bits of her are alive everywhere. She is the originator of the first immortal cell line, HeLa cells. These are cancer cells scraped from her cervix, and they grew so well that they proved ideal for study in laboratories all over the world. Unfortunately, they grew so well in culture that they invaded other cell lines and ruined countless experiments. It became such a problem that in 1968, the premier standard-bearer of cell lines in the world, the American Type Culture Collection, tested all thirty-four of its "pure" cell lines and found that twenty-four of them were HeLa cells instead.

cancer The term ‘cancer’ refers to a diverse group of diseases, characterized by uncontrolled growth of cells, leading to a variety of pathological consequences and frequently death. It is typically a disease of the elderly — the incidence of all forms of cancer increases markedly with age. However, it also occurs occasionally in children. Often the abnormal cell growth results in the establishment of a macroscopic lump or tumour ‘oncos’ in Greek, hence the term ‘oncology’ for the study of cancer), which may grow to a large size and kill the patient by a local effect, e.g. occlusion of vital ducts — even the alimentary tract — or by compromising the functioning of some distant organ. Indeed, the very word ‘cancer’ derives from the appearance of solid tumours as noted on post mortem examination by early physicians, who likened their appearance to that of a crab (Cancer) because of the irregular and disorganized appearance of the threads of the tumour radiating from a central body. Some forms of cancer, however, do not grow as coherent lumps but as individual cells diffused through the vascular system; these diseases — leukaemias and lymphomas — are associated with quite a different pathological profile.

Not all tumours of the human body are cancerous, however. Everyone is familiar with the common wart, and probably other skin lesions that result from local proliferation of cells, and which are quite benign. What distinguishes cancerous tumours and renders them seriously life-threatening is the property of malignancy, which derives from the capacity of the cells to invade surrounding tissue and to break off from the parent lump, migrate around the body in the blood vessels or the lymphatic system, and set up secondary foci of cancerous growth at distant sites. It is the latter phenomenon, metastatic spread of the disease, which most frequently kills cancer patients. The secondary foci — metastases — often occur in the brain, lungs, or liver, because these organs have a large blood supply and a well-developed capillary bed of tiny vessels in which single cancer cells or clumps of cells can lodge. By contrast, many common skin cancers (with the singular exception of malignant melanoma) are invasive but not metastatic, so they can be cured by simple excision of the tumour together with a decent margin of surrounding tissue. This emphasizes the seriousness of metastasis in the pathology of cancer. It is also salutary that in many instances cancer patients present with clear evidence of metastatic disease, such as secondary tumours radiologically visible in the lung, but no sign of the primary lump. It may take all the skill of an experienced histopathologist to indicate the probable origin of the diseased cells, knowledge of which is likely to be crucial for any form of clinical management.

Cancer therapy involves four modalities which may be employed singly or in combination: surgery, radiotheraphy, chemotherapy, or a group of less well-defined treatments, of which immunotherapy is the chief example. It is common practice to employ surgery where applicable (to reduce the tumour burden if a single large mass has been detected e.g. by X-rays or magnetic resonance imaging), followed by localized or whole-body radiotherapy to attack residual disease, and/or chemotherapy to deal with distant metastases. If the disease is advanced, with obvious metastasis, chemotherapy with a cocktail of three or four powerfully cytotoxic drugs may be the only worthwhile option. Most of these drugs are DNA-reactive chemicals which directly attack the genetic blueprints of the rogue cells. Alternatively a massive dose of whole-body irradiation may be attempted, and the patient rescued from death due to destruction of his bone marrow by subsequent reimplantation of his own marrow cells, collected prior to treatment and ‘cleaned up’ in vitro (autologous bone marrow transplantation).

Cancer is increasingly seen as a lifestyle disease, caused at least partly by environmental influences, with important modulation by the genetic inheritance of the individual. Sometimes viral infections may start the process off. In other cases sunlight is to blame, particularly in causing skin cancers among fair-skinned Caucasians living in tropical countries or under the ozone hole of the Southern hemisphere. Sometimes it is diet which seems to trigger disease, especially of the gastrointestinal tract: here fats are held suspect, and a high-fibre diet rich in cereals and vegetables is to be recommended. But far and away the most serious, and preventable, environmental cause of cancer is tobacco smoking, which is inexorably linked to cancer of the lung. On this conclusion the epidemiological evidence is stark — witness the sharp continuing rise in lung cancer among women in the Western world, which correlates precisely with the changes in social attitudes to smoking over the last 50 years.

One of the hottest areas of cancer research by the end of the twentieth century was the identification of genes that impart an inherited susceptibility to cancer of particular organs, or to cancer in general. Early successes have been the discovery of BRCA1 and BRCA2, genes which predispose to breast cancer — still the most common form of malignancy in Western women — and there are more to come. Other cancer-prone individuals carry genes whose products are enzymes known to be intimately associated with the biological phenomena of cell signalling, gene transcription, or DNA repair. A picture is beginning to emerge of cancer development, starting with a single cell exposed to some external influence, which causes a mutation in one of a small number of critical genes, ‘initiating’ the process of escape from growth control. Other genetic changes, leading to aneuploidy (abnormalities in the nature or the number of chromosomes), follow over a period which may be as long as several years, while so-called ‘promoter’ substances exacerbate the multiplication of the abnormal cells into a small tumour, which begins to invade its surroundings and may start to metastasise. In the later stages of disease the cells enter a ‘progression’ phase, in which gross rearrangements of their genetic make-up occur — these, can be seen down the microscope as wholesale redistribution of chromosomes, involving deletions, translocations, breaks, duplications, and doubtless many more subtle changes. Genetic instability can proceed to a state of chromosomal chaos — a ‘point of no return’ whereby cells cannot revert to the normal karyotype (the characteristics of its chromosomes) and must be killed. At that stage the disease is rampant and only the most aggressive intervention, including treatment with drugs which have dire toxic side-effects, is likely to produce any relief or remission, and cure is most unlikely. Often the side-effects (hair loss, vomiting and diarrhoea, neurological disorders, or bone marrow suppression) are so serious as to be unacceptable to the sick patient, and palliative treatment with powerful opiates is all that can be recommended. The most recent scientific findings emphasize the importance in tumour control of programmed cell death (apoptosis) and shortening of the far end, of the ‘arms’ of chromosomes (the telomeres) during replication. Chemotherapeutic and radiotherapeutic strategies induce apoptosis, so escape from programmed death signals is important.

M. J. Waring

CANCER

CANCER remains one of the most feared diseases of our times. Every year 500,000 Americans die from tumors of one sort or another, up from about 30,000 at the beginning of the twentieth century. Part of the increase is due to population growth and the fact that people now live longer—and cancer is, generally speaking, a disease of the elderly. A smaller fraction of the increase is due to the fact that previously undetected cancers are now more likely to be diagnosed. But cancer risks have also grown over time, due to increased exposures to carcinogenic agents—notably New carcinogens in food, air, and water, such as pesticides and asbestos; the explosive growth of tobacco use in the form of cigarettes, which were not widely used until World War I; and exposure to various forms of radiation, such as X-rays and radioisotopes. Tobacco alone still causes nearly a third of all American cancer deaths—including 90 percent of all lung tumors—making it the single most important cause of preventable cancers.

Cancer is actually a cluster of several different diseases, affecting different parts of the body and different kinds of tissue. Leukemia is a cancer of the blood, myeloma a cancer of the bone marrow, melanoma a cancer of the skin, and so forth. Cancer can be seen as "normal" tissue growing out of control or in places where it should not. In the case of breast cancer, for example, the danger is not from cancer cells confined to the breast, but rather from cancerous breast cells spreading to other parts of the body ("metastasis"), where they grow and eventually interfere with other parts of normal bodily function. Cancerous growths seem to begin when the body's normal cellular "suicide" functions break down; malignant cells are immortal in the sense that they continue to divide instead of periodically dying off as healthy cells should.

A great deal of research has gone into exploring the genetic mechanisms of carcinogenesis, with the hope of finding a way to halt the growth of cancerous cells. The difficulty has been that cancer cells look very much like normal cells, the difference typically being only a few minor mutations that give the cell novel properties. That is why cancer is so difficult to treat. It is not like the flu or malaria, where a living virus or bacterium has infected the body. Cancer cells are often not even recognized as foreign by the body's immune system—which is why they can grow to the point that normal physiological processes are obstructed, causing disability and, all too often, death.

Cancer also has to be understood as a historical disease, since the kinds of cancer that are common in a society will often depend on what people eat or drink, what kinds of jobs or hobbies or habits are popular, what kinds of environmental regulations are enforced, the environ-mental ethics of business leaders and labor activists, and many other things as well. Cancer is a cultural and political disease in this sense—but also in the sense that different societies (or different people within the same society) can suffer from very different kinds and rates of cancer.

Stomach cancer was the number one cause of cancer death in America in the early years of the twentieth century, for example, accounting for about half of all American cancer deaths. By the 1960s, however, stomach cancer had fallen to fifth place in the ranks of cancer killers, as a result of food refrigeration and the lowered consumption of high-salt, chemically colored, and poorly preserved foods. Cancers of the lung, breast, and ovary are now the more common causes of death for women, as are cancers of the lung, colon, prostate, and pancreas among men. Lung cancer has become the leading cause of cancer death among both men and women, in consequence of the rapid growth of smoking in the middle decades of the twentieth century. The twenty-to thirty-year time lag between exposure and death for most cancers explains why the decline of smoking in the 1970s and 1980s only began to show up at the end of the century in falling lung cancer rates.

It is important to distinguish cancer mortality (death rates) from cancer incidence (the rates at which cancers appear in the population). Some cancers are fairly common—they have a high incidence—but do not figure prominently in cancer mortality. Cancer of the skin, for example, is the most common cancer among both men and women, but since few people die from this ailment, it does not rank high in the mortality tables. Most skin cancers are quite easily removed by simple surgery. Lung cancer survival rates, by contrast, are quite low. Mortality rates are tragically close to incidence rates for this particular illness.

Worries over growing cancer rates led President Richard Nixon to declare a "war on cancer" in his State of the Union address of 1971. Funding for cancer research has increased dramatically since then, with over $35 billion having been spent by the National Cancer Institute alone. Cancer activists have also spurred increased attention to the disease, most notably breast cancer activists in the 1980s and prostate cancer activists in the 1990s. Attention was also drawn to Kaposi's sarcoma from its association with AIDS. Cancer researchers have discovered a number of genes that seem to predispose certain individuals to certain kinds of cancer; there are hopes that New therapies may emerge from such studies, though such knowledge as has been gained has been hard to translate into practical therapies. Childhood leukemia is one case where effective therapies have been developed; the disease is now no longer the death sentence it once was. From the point of view of both policy and personal behavior, however, most experts agree that preventing cancer is in principle easier than treating it. Effective prevention often requires changing deeply ingrained personal habits or industrial practices, which is why most attention is still focused on therapy rather than on prevention.

We already know enough to be able to prevent about half of all cancers. The problem has been that powerful economic interests continue to profit from the sale of carcinogenic agents—like tobacco. With heart disease rates declining, cancer will likely become the number one cause of American deaths by the year 2010 or 2020. Global cancer rates are rapidly approaching those of the industrialized world, largely as a result of the increasing consumption of cigarettes, which many governments use to generate tax revenue. The United States also contributes substantially to this global cancer epidemic, since it is the world's largest exporter of tobacco products. Only about two-thirds of the tobacco grown in the United States is actually smoked in the United States; the remainder is exported to Africa, Europe, Asia, and other parts of the world. Cancer must therefore be regarded as a global disease, with deep and difficult political roots. Barring a dramatic cure, effective control of cancer will probably not come until these political causes are taken seriously.

BIBLIOGRAPHY

Epstein, Samuel S. The Politics of Cancer Revisited. Fremont Center, N.Y.: East Ridge Press, 1998.

Patterson, James T. The Dread Disease: Cancer and Modern American Culture. Cambridge, Mass.: Harvard University Press, 1987.

Proctor, Robert N. Cancer Wars: How Politics Shapes What We Know and Don't Know About Cancer. New York: Basic Books, 1995.

Robert N.Proctor

See alsoCenters for Disease Control and Prevention ; Smoking ; Tobacco Industry .

Cancer

Normal tissue development depends on a balance between cell multiplication and cell death. When cells multiply faster than they die, the result is an abnormal tissue growth called a tumor (neoplasm). The study and treatment of tumors is a branch of medicine called oncology.

Not all tumors are cancerous. Benign tumors are surrounded by a fibrous capsule, grow slowly, and do not spread to other organs; although they are nevertheless sometimes fatal. A wart is a benign tumor. Malignant tumors have no capsule, grow rapidly, and shed cells that can "seed" new tumors in other organs, a phenomenon called metastasis . The word cancer refers only to malignant tumors. The word literally means "crab." It was coined by the ancient Greek physician Hippocrates when the tangle of blood vessels in a breast tumor reminded him of the legs of a crab.

Cancers are classified according to the type of tissues or cells in which they originate (see Table on page 112). A primary tumor is a tumor in the site of origin, and a secondary (metastatic) tumor is a tumor in a new site resulting from the spread of cells from the original tumor, for example, a brain tumor resulting from cells that originated in colon cancer.

Causes of Cancer

Most cancer is caused by environmental agents called carcinogens. Carcinogens include chemicals such as cigarette tar, nitrites (used as food preservatives), and many industrial chemicals; viruses such as the hepatitis B and herpes simplex 2 viruses; and ionizing radiation such as X rays and gamma rays. All of these agents are mutagens; that is, they cause mutations, or changes in deoxyribonucleic acid (DNA) and chromosome structure, which in turn result in uncontrolled cell division.

Cancer Genes

The risk of cancer is often hereditary, and many forms of cancer have been traced to two types of genes : oncogenes and tumor-suppressor genes.

Oncogenes. Oncogenes are mutated, "misbehaving" genes that normally code for growth factors or their receptors. Growth factors are chemical signals that trigger cell division. Some oncogenes cause excessive secretion of growth factors, and thus excessive cell division. Other oncogenes code for dysfunctional receptors that act like switches stuck in the "on" position, sending signals for cell division even when there is no growth factor bound to them. Many cases of breast and ovarian cancer are due to an oncogene called erbB2.

Tumor-Suppressor Genes. Tumor-suppressor (TS) genes normally inhibit cancer by opposing the action of oncogenes, promoting the repair of mutated DNA, or controlling tissue development. When TS genes are mutated, these protections are lost. A TS gene called p53 has been implicated in leukemia and colon, lung, breast, liver, brain, and esophageal cancer.

The top ten causes of cancer mortality in the United States, ranked from highest to lowest, are cancers of the lung, colon, breast, prostate, pancreatic, leukemic, ovarian, stomach, nervous system, and bladder.

Thus, oncogenes promote cancer and TS genes suppress it. They can be loosely compared to the accelerator and brake on a car, respectively. A defect in either one causes the "car," cell division, to run out of control. Cancers typically require more than one mutation before they develop; thus, colon cancer involves damage to at least three TS genes on chromosomes 5, 17, and 18, plus activation of an oncogene on chromosome 12. It may take many years for so many mutations to accumulate in a single cell, which is one reason cancer is more common among the elderly than among young people.

Effects of Cancer

Cancer is almost always fatal if it is not treated. Four ways in which cancer can kill are:

1. By displacing normal tissue, so the function of an organ deteriorates; an example of this is when a lung tumor replaces so much lung tissue that the blood can no longer get enough oxygen, or a brain tumor compresses and kills brain tissue
2. By invading blood vessels, causing fatal hemorrhages
3. By compressing vital passages, for example shutting off air flow into the lung or obstructing blood flow through a major vein or artery
4. By competing with healthy tissues for nutrients, often causing the body to break down its own proteins (muscle, for example) to feed the "hungry" tumor, or failing to make enough red blood cells and platelets because stem cells are diverted into producing the abnormal white blood cells of leukemia.

Cancer is normally treated by surgery, chemotherapy, or both, depending on its location, type, and extent. Other approaches are radiotherapy (using radiation to destroy tumors) and immunotherapy (providing antibodies or immune cells to attack cancer cells). Some forms of cancer are highly treatable, such as skin cancer, whereas others offer much less hope of recovery, such as pancreatic cancer.

see also Cell Cycle; Genetic Diseases; Mutation; Oncogenes and Cancer Cells

Kenneth S. Saladin

Bibliography

American Cancer Society. <http://www.cancer.org/>.

Fauci, Anthony S., et al. Harrison's Principles of Internal Medicine, 14th ed. New York: McGraw-Hill, 1998.

McCance, Kathryn L., and Sue E. Huether. Pathophysiology, 3rd ed. St. Louis: Mosby, 1998.

Varmus, H., and R. A. Weinberg. Genes and the Biology of Cancer. San Francisco: W. H. Freeman and Company, 1993.

66. Cancer

See also 122. DISEASE and ILLNESS .

adenocele

a cystic tumor that may develop in the glands.

adenosarcoma

a malignant glandular tumor of the soft tissues of the body.

astroblastoma

a malignant tumor that may invade the brain and spinal cord, especially investing blood vessels.

astrocytoma

a brain tumor composed of large, star-shaped cells called astrocytes.

blastoma

a neoplasm arising in the blastema, i.e., tissue from which an organ or part is formed. Also blastocytoma.

cancericidal

of or pertaining to a chemical or process than can destroy malignant cells.

cancerophobia

carcinomophobia.

cancroid

1. of or pertaining to a lesion that resembles cancer.

2. a malignant skin cancer.

carcinectomy

the surgical removal of a cancer.

carcinogen

any natural or artificial substance that can produce or trigger cancer, as arsenic, asbestos, ionizing radiation, ultraviolet rays, x rays, and many derivatives of coal tar. —carcinogenic, adj.

carcinoid

a small, yellow tumor that may develop from argentaffin cells in the gastrointestinal mucosa and spread widely throughout the body.

carcinolysis

the destruction of malignant cells, as by an antineoplastic drug.

carcinoma

1. a malignant tumor that may spread to surrounding tissue and distant areas of the body.

2. any kind of epithelial cancer. —carcinomatous, adj.

carcinomatosis

carcinosis.

carcinomophobia, carcinomatophobia, carcinophobia

an abnormal fear of cancer. Also called cancerophobia.

carcinophilia

an afflnity for cancerous tissue, a property of certain chemical agents. —carcinophilic, adj.

carcinosis

1. an abnormal condition characterized by the growth of numer-ous carcinomas throughout the body. Also carcinomatosis.

2. the process of development of carcinoma.

carcinostatic

of or pertaining to the slowing or stopping of the growth of a carcinoma.

celiothelioma

mesothelioma.

cerebroma

any abnormal mass of brain tissue, malignant or benign.

chemosurgery

a therapeutic procedure that uses chemicals to destroy pathogenic tissue, especially skin cancers.

chemotherapy

a procedure that uses radioisotopes of various elements, as iodine, phosphorus, and gold, to treat cancers of the thyroid gland, lungs, and other organs.

chloroma

a malignant, greenish tumor that invades myeloid tissue and fluoresces red under ultraviolet light.

chondrocarcinoma

a malignant cartilageous tumor of the epithelium.

chondrosarcoma

a malignant cartilageous tumor that most frequently invades the long bones, pelvis, and the scapula.

chordoma

a rare congenital tumor of the brain.

chorioblastoma

choriocarcinoma.

choriocarcinoma

a uterine malignancy that may develop shortly after conception, during pregnancy, or after an abortion. Also called chorioblastoma, chorionic epithelioma .

comedocarcinoma

a malignant tumor of the mammary ducts.

cystoma

any neoplasm or tumor that contains cysts, especially any such tumor that invades the ovaries.

cytotechnology

the study of human cells, especially to detect signs of cancer. —cytotechnologist, n. —cytotechnolqgic, adj.

erythroleukemia

a malignancy of the blood characterized by abnormally productive bone marrow and the development of oddly-shaped blood cells.

glioma

any of the predominant category of brain tumors composed of cancerous glial cells (a type of nerve cell).

hepatoma

a malignant tumor of the liver that most commonly occurs in association with hepatitis or cirrhosis,

leukemia

a malignancy of blood-producing tissues, characterized by proliferating immature white blood cells and infiltration of the spleen, liver, and other organs. Also leukocythemia. —leukemie, leukemoid, adj.

leukocythemia

leukemia.

liposarcoma

a cancerous growth of primitive fat cells. Also called lipoma sarcomatode.

lymphoma

a growth of lymphoid tissue that is commonly cancerous and typically enlarges the lymph nodes.

medulloblastoma

a malignant tumor that commonly originates in the cere-bellum.

melanoma

any malignant growth, especially in the skin, that is composed of melanin-producing cells.

mesothelioma

a rare malignant tumor that may invade the linings of the lungs and the abdomen. Also called celiothelioma.

metastasis

the spread of malignancies, characterized by the cancerous invasion of the lymphatic system, the blood, and body organs. —metastatic, adj. —metastasize, v.

neoplasia

the abnormal proliferation of benign or malignant cells. —neoplastic, adj.

neoplasm

the abnormal development of benign or cancerous tissue. —neoplastic, adj.

neurinoma

a tumor that develops in a neural sheath and that may become malignant.

neuroblastoma

a highly malignant tumor that may develop from the neural plate in an embryo and spread to the bones, liver, and other organs.

neurosarcoma

a malignant growth composed of neural, connective, and vascular tissues. Also called malignant neuroma.

oncogenesis

the process by which a tumor develops. —oncogenic, adj.

oncology

the field of medicine that specializes in the study of tumors.

osteoclastoma

a giant cell bone tumor that most commonly develops at the end of a long bone.

osteosarcoma

a malignant bone tumor. Also called osteogenic sarcoma .

retinoblastoma

a common childhood malignancy of the eye that develops from retinal cells.

sarcoma

a rare malignant tumor of the soft tissues that commonly develops in the lower extremities.

ulocarcinoma

a malignancy of the gums.

Cancer. Cancers are malignant tumors or malignancies that arise in bone marrow or lymph nodes and spread to other tissues or organs. The oldest cancers in the Americas are those found in the bones of fossilized dinosaurs; cancers no doubt also afflicted the earliest human beings on the continent, who arrived about twelve thousand years ago. Little is known about cancer rates prior to the nineteenth century, though lip and lung cancers were probably not uncommon among native smokers of tobacco. Natural sources of radiation—like radon or ultraviolet solar radiation—must also have contributed to the occasional lung or skin cancer, though cancer rates as a whole were probably lower than those for subsequent generations of European colonists.

John Le Conte (1818–1891), a professor of physics at the University of California after the Civil War, was one of the first Americans to suggest that cancer was on the rise. Le Conte portrayed cancer as a “disease of civilization,” though it did not surpass tuberculosis as a cause of U.S. mortality until the 1920s. (Heart disease was already in first place, a position it held through the twentieth century.) One reason for the transition was that life expectancy was increasing, pushing more people into the cancer‐prone years. Age‐adjusted mortality rates began to be calculated about this time, though statistical record‐keeping remained rudimentary. Federal mortality statistics did not distinguish among different kinds of cancer until the early twentieth century; the first population‐based registry was not established until 1937, in Connecticut.

Cancer rates grew rapidly after World War II, bucking the trend of diseases—like syphilis and poliomyelitis—that were succumbing to scientific medicine. Funding for the U.S. National Cancer Institute, established in 1937, increased dramatically in the 1950s, but environmental or lifestyle causes of cancer received little attention. Wilhelm Hueper's Occupational Tumors and Allied Diseases (1942) set the stage for the view that “the environment”—including diet and tobacco products—was responsible for most human cancers, a view later endorsed by the World Health Organization (Prevention of Cancer, 1964).

Rachel Carson's widely read Silent Spring (1962)—based partly on Hueper's work—fueled the idea that environmental pollution might be partly to blame for increasing cancer rates, though epidemiological studies by Richard Doll, A. Bradford Hill, and Ernst Wynder in the early 1950s showed that cigarettes bore responsibility for most of the increase. The U.S. surgeon general in 1964 identified tobacco as a major cause of cancer; smoking rates for men peaked at about that time, though lung‐cancer rates would continue to rise for another quarter of a century. Lung cancer had become the leading cause of cancer death among males by the early 1950s; among women, mortality from lung cancer did not surpass breast cancer mortality until the 1980s.

President Richard M. Nixon in his 1971 State of the Union address declared a “war on cancer”; the National Cancer Act of that same year signaled major increases in research funds devoted to cancer. The National Cancer Institute became the largest single unit of the National Institutes of Health, reporting directly to the president, with an annual budget that surpassed two billion dollars by the 1990s. Many scientists hoped that a cancer vaccine might be found to eliminate the disease, as had been the case with polio and smallpox.

In the 1970s, labor and environmental activists such as Samuel Epstein (The Politics of Cancer, 1978) began to protest the failure of the National Cancer Institute to address the causes of cancer in a manner that might lead to effective prevention. Lung cancers and other internal tumors began to appear in tens of thousands of asbestos workers, especially shipyard workers who had sprayed the mineral inside ships in World War II. Widely publicized cases of cancers caused by vinyl chloride, benzene, dry‐cleaning fluids, hair dyes, and other petrochemicals gave rise to the widespread and controversial notion that the modern chemical environment was causing unprecedented numbers of cancers.

Cancer rates continued to climb until the early 1990s, by which time the decline in smoking was resulting in lower cancer rates. Cancer mortality rates fell by about 3 percent from 1990 to 1995, the first clear drop since data had begun to be recorded. Cancer rates remained particularly high for African Americans, though most observers believed the inequality had more to do with environmental factors relating to poverty than with race‐specific organic factors. As the twentieth century ended, cancer rates had still not fallen as much as deaths from heart attack, apparently because treatments for heart failure had improved much more rapidly than treatments for cancer. Projections suggested that cancer would become the number‐one cause of U.S. deaths sometime early in the twenty‐first century.
See also Disease; Environmentalism; Food and Diet; Medicine; Tobacco Industry; Tobacco Products.

Bibliography

Richard Doll and and Richard Peto , The Causes of Cancer, 1981.
James T. Patterson , The Dread Disease: Cancer and Modern American Culture, 1987.
Robert N. Proctor , Cancer Wars: How Politics Shapes What We Know and Don't Know about Cancer, 1995.

Robert N. Proctor

Paul S. Boyer

Cancer

Cancer is a disease of uncontrolled cell growth caused by exposure to carcinogens (cancer-causing substances), genetic defects, or viruses. Cancer cells can multiply and form a large mass of tissue called a tumor. Some tumors are limited to one location and can be surgically removed. These tumors may cause little harm and are therefore termed benign. Cancer cells of other tumors may spread, or metastasize (muh-TASS-tuh-size), to surrounding tissue or other organs of the body. Such aggressive tumors are termed malignant. Cancer is a word used usually to describe malignant, not benign, tumors. The study of cancer is called oncology.

How cancer cells are formed

The transformation of a normal cell into a cancer cell can occur when the genetic material (deoxyribonucleic acid or DNA) of a cell is changed, or mutated. A tumor is the result of multiple gene mutations within a single cell. Years or decades before a tumor forms, a cell can become weakened by various factors, making it more susceptible to later transformation into a cancer cell. Cancer is often a disease of age, with many occurring after age fifty.

Types of cancer

There are more than 200 different types of cancer, and they are named for the organ or tissue in which they begin to grow. Leukemia refers to cancer of white blood cells (also called leukocytes), and lymphoma is cancer of lymphoid tissue (a connective tissue containing white blood cells called lymphocytes). Melanomas are cancers that begin in melanocytes (skin pigment cells). Cancers that originate in epithelial tissue (cellular tissue that lines cavities such as the stomach or lung) are called carcinomas. Those that begin in connective tissue (such as bone and cartilage) or muscle are called sarcomas.

Words to Know

Carcinogen: A substance capable of causing cancer.

Chromosome: Organized strands of DNA in the nucleus of a cell.

DNA (deoxyribonucleic acid): The genetic material in the nucleus of cells that contains information for an organism's development.

Gene: A section of a chromosome that carries instructions for the formation, functioning, and transmission of specific traits from one generation to another.

Mutation: A change in the DNA in a cell.

Tumor: A mass of abnormal tissue that can be malignant or benign.

Causes of cancer

One of the most carcinogenic substances known is tobacco smoke. It is the major cause of lung cancer, which is the leading cause of cancer deaths in both men and women in the United States. In the year 2000, almost 160,000 people in the United States died from lung cancer. In comparison, cancer of the colon and rectum caused over 56,000 deaths that same year. Breast cancer claimed over 41,000 lives, while prostate cancer claimed almost 32,000.

Other carcinogens include certain chemicals, the Sun's ultraviolet light, and radiation. Some viruses can cause cancer by altering the DNA of a host cell and converting the cell's normal genes into cancer-causing genes, or oncogenes. Genetic factors—such as chromosomal

abnormalities or the inheritance of faulty genes from a parent—can make some people more likely to develop certain cancers. For instance, people with Down syndrome, a chromosomal abnormality, are susceptible to leukemia.

Treatment

Cancer treatment consists of surgery to remove tumors and radiation to slow tumor growth. Chemotherapy, or drug therapy, is often used to treat cancers that have spread to other parts of the body. Another approach to treatment is to boost the immune system with immune-enhancing drugs or antibodies that can recognize and destroy abnormal cells. A new type of anticancer drug that homes in on cancer cells—leaving healthy ones alone—was introduced in the spring of 2001. The drug, Gleevec, works strikingly well against chronic myelogenous leukemia (one of the four main types of blood cancer) and gastrointestinal stromal tumor (GIST; a rare stomach tumor). Scientists believe the future of cancer treatment lies in the development of a wider range of anticancer drugs and in genetic engineering, whereby healthy genes would be manufactured to replace mutated DNA in transformed cells.

Prevention

Many cancers are preventable. It is estimated that avoidance of tobacco, overexposure to the Sun, high-fat diets, excessive alcohol, unsafe sex, and other known carcinogens could prevent more than 80 percent of all cancer cases. In addition, yearly testing can detect certain cancers and make early treatment possible, providing a better chance of survival.

[See also Carcinogen; Nucleic acid ]

cancer Any disorder of cell growth that results in invasion and destruction of surrounding healthy tissue by abnormal cells. Cancer cells arise from normal cells whose nature is permanently changed. They multiply more rapidly than healthy body cells and do not seem subject to normal control by nerves and hormones. They may spread via the bloodstream or lymphatic system to other parts of the body, where they produce further tissue damage (metastases). Malignant tumour is another name for cancer. A cancer that arises in epithelium is termed a carcinoma; one that arises in connective tissue is called a sarcoma. Leukaemia is cancer of white blood cells; lymphoma is cancer of lymphoid tissue; and myeloma is cancer of plasma cells of the bone marrow. Causative agents (carcinogens) include various chemicals (including those in tobacco smoke), ionizing radiation, silica and asbestos particles, and oncogenic viruses. Hereditary factors and stress may also play a role. See oncogene.

Can·cer / ˈkansər/ 1. Astron. a constellation (the Crab), said to represent a crab crushed under the foot of Hercules. It is most noted for the globular star cluster of Praesepe (the Beehive cluster). ∎  [as genitive] (Can·cri / ˈkangkrē/ ) used with a preceding letter or numeral to designate a star in this constellation: the star Delta Cancri. 2. Astrol. the fourth sign of the zodiac, which the sun enters at the northern summer solstice (about June 21). ∎  (a Cancer) a person born when the sun is in this sign. PHRASES: tropic of Cancersee tropic¹ . DERIVATIVES: Can·cer·i·an / kanˈsərēən; -ˈsi(ə)r-/ n. & adj. (in sense 2).

cancer (kan-ser) n. any malignant tumour, including carcinoma and sarcoma. It arises from the abnormal and uncontrolled division of cells that then invade and destroy the surrounding tissues. The cancer cells spread (see metastasis), setting up secondary tumours (metastases) at sites distant from the original tumour. There are probably many causative factors, some of which are known; for example, cigarette smoking is associated with lung cancer, radiation with some sarcomas and leukaemia, and several viruses are implicated; genetic factors are involved in the development of many cancers. Treatment of cancer depends on the type of tumour, the site of the primary tumour, and the extent of spread.


www.cancerresearchuk.org Website of Cancer Research UK

CANCER

DEFINITION

Cancer is not just one disease, but a group of almost one hundred diseases. These diseases have two common characteristics. First, cells begin to grow out of control in the body. Second, those cells have the ability to travel from their original site to other locations in the body. If the spread is not controlled, cancer can result in death.

DESCRIPTION

Cancer is responsible for one out of every four deaths in the United States. It is second only to heart disease as a cause of death in this country. About 1.2 million Americans were diagnosed with cancer in 1998. Of that number, more than 500,000 are expected to die of the disease.

Cancer can attack anyone, but the chances of getting the disease increase with age. The most common forms of cancer are skin cancer, lung cancer, colon cancer, breast cancer (in women; see breast cancer entry), and prostate cancer (in men; see prostate cancer entry). Other major cancers that affect Americans include those of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and blood and lymph nodes (see leukemia entry).

Cancer is a disorder that affects the genes. A gene is a small part of a deoxyribonucleic (pronounced dee-OK-see-RIE-bo-noo-KLEE-ik) acid (DNA) molecule. DNA molecules carry the master plan in cells that tells them how to behave. Genes carry the directions for making proteins. Proteins are involved in a wide number of functions in the body that make it possible to move, think, breathe, and carry out other activities.

Normally, cells go through a cycle in which they grow, divide, and die. Gene mutations (changes) can interrupt that cycle. Cells forget how to stop growing and reproduce over and over again, forming a lump of cells that gets bigger and bigger. The lump is known as a tumor or neoplasm ("new growth," pronounced NEE-o-plaz-um).

A healthy person's immune system can usually recognize and destroy neoplastic cells. Sometimes, though, mutant cells can escape detection. When they do, they can go on to become tumors. Tumors are of two types: benign ("harmless," pronounced bih-NINE) and malignant (harmful and possibly terminal, pronounced muh-LIG-nent). Benign tumors grow slowly and do not spread in the body. Once removed, they usually do not reappear. Malignant tumors, by contrast, invade surrounding tissue and spread through the body. If removed, a malignant tumor often grows back.

Most gene mutations are caused by environmental factors called carcinogens (pronounced car-SIN-o-genz). Carcinogens are things in our environment that cause cancer. Many kinds of carcinogens are known.

Cancer: Words to Know

Benign:

A growth that does not spread to other parts of the body, making recovery likely with treatment.

Biopsy:

Surgical removal and microscopic examination of tissue for diagnostic purposes.

Bone marrow:

Spongy material that fills the center of bones, from which blood cells are produced.

Carcinogen:

Any substance capable of causing cancer.

Chemotherapy:

Treatment of cancer that uses chemicals or drugs that destroy cancerous cells or tissues.

Epithelium:

The layer of cells covering the body's outer and inner surfaces.

Hormone therapy:

Treatment of cancer by slowing down the production of certain hormones.

Immunotherapy:

Treatment of cancer by stimulating the body's immune system.

Malignant:

Cancer cells that have broken loose from a tumor and spread to other parts of the body.

Metastasis:

The process by which cancer cells have spread from their original source to other parts of the body.

Radiation therapy:

Treatment that uses various forms of radiation to kill cancer cells.

Tumor:

An abnormal growth that has developed as cancer cells grow out of control.

X rays:

A kind of high-energy radiation that can be used to take pictures of the inside of the body, to diagnose cancer, or to kill cancer cells.

Some kinds of cancer are caused by genetic factors. Faulty genes can be passed from parents to children. When that happens, the children are at risk for cancer. In most such cases, a cancer is caused by some combination of genetic and environmental factors.

Normal body characteristics can increase the likelihood that a person will develop cancer. For example, people with fair skin are more likely to get skin cancer (see skin cancer entry) than those with darker skin.

Cancers can be classified according to the part of the body in which they occur:

• Carcinomas. Carcinomas (pronounced car-sen-O-muhz) are cancers that arise in the epithelium (pronounced eh-peh-THEE-lee-um). The epithelium is the layer of cells that covers the outside (the skin) and the inside of the body. Carcinomas covering the exterior epithelium are called squamous (pronounced SKWAY-muss) cell carcinomas. Those that develop in an organ or gland are called adenocarcinomas (pronounced add-en-o-car-sen-O-muhz).
• Melanomas. Melanomas are another form of skin cancer, and usually occur in cells that give skin their color (melanocytes).
• Sarcomas. Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle, and blood vessels.
• Leukemias. Leukemias are cancers of the blood.
• Lymphomas. Lymphomas are cancers of the lymph system.
• Gliomas. Gliomas are cancers of nerve tissue.

CAUSES

The major risk factors for cancer are tobacco and alcohol use, diet, sexual and reproductive behavior, infectious agents, family history, occupation, radiation, and pollution.

The American Cancer Society estimates that about 40 percent of all cancer deaths in the United States are caused by tobacco and excessive alcohol use. An additional one-third of the deaths are caused by poor diet and nutrition. The vast majority of deaths from skin cancer are due to overexposure to ultraviolet light in the sun's rays.

Tobacco

Smoking is responsible for 80 to 90 percent of all cases of lung cancer (see lung cancer entry). Smoking is also a factor in other forms of cancer affecting the upper respiratory (breathing) tract, larynx, bladder, pancreas, and, probably, liver, stomach, and kidney. Secondhand smoke (smoke exhaled by smokers and inhaled by others nearby) can also increase the risk of developing cancer.

Alcohol

People who drink too much alcohol are at risk for certain forms of cancer, such as liver cancer. In combination with smoking, the use of alcohol can also increase the risk of developing cancer of the mouth, pharynx (pronounced FAHR-inks), larynx, and esophagus (pronounced SAH-fuh-guss).

Diet

One in three cancers can be traced to dietary factors. Obesity (see obesity entry) has been connected with cancers of the breast, colon, rectum, pancreas, prostate, gallbladder, ovaries, and uterus.

Sexual and Reproductive Behaviors

Some cancer-causing viruses can be transmitted by sexual activity. People who begin sexual activity early in their lives and have many partners appear to have a higher risk for developing cancer. Women who never have children or have them late in life may be at higher risk for developing ovarian and breast cancer.

Infectious Agents

Scientists believe that about 15 percent of all cancers are caused by viruses, bacteria, or parasites. A list of the most common cancer-causing infectious agents is shown in the table below.

Family History

Certain forms of cancer recur generation after generation in some families. These include breast, colon, ovarian, and uterine cancers.

Occupational Hazards

About 4 percent of all cancers are thought to be connected with one's occupation. For example, people who work with asbestos have an increased chance of developing lung cancer. Asbestos is a naturally occurring mineral that was once used widely as insulation for housing and other buildings. Many other forms of occupational cancer have been identified. These include:

• Bladder cancer, among dye, rubber, and gas workers
• Skin and lung cancer, among those who work in smelters, with arsenic, and in gold mines
• Leukemia, among glue and varnish workers
• Liver cancer, among workers in the PVC (polyvinyl chloride plastics) industry
• Lung, bone, and bone marrow cancer, among people who work with X rays and other forms of radiation, or with uranium

Radiation

Ultraviolet radiation is responsible for the majority of deaths from melanoma. Other sources of radiation include X rays, radon gas, and radiation from nuclear materials. These sources combined are thought to be responsible for about 1 to 2 percent of all cancer deaths.

Pollution

Experts think that roughly 1 percent of all cancer deaths are caused by air, land, and water pollution. Industries that release harmful chemicals into the environment are the primary source of these pollutants.

SYMPTOMS

Cancer is a progressive disease. That is, it goes through a series of stages that are progressively worse. The symptoms are different at each stage. One of the earliest symptoms of cancer is pain. As tumors grow, they push on organs, nerves, blood vessels, and other tissues around them, causing pain.

The earlier cancer is detected, the more effectively it can be treated. For this reason, the American Cancer Society has prepared a list of seven warning signs of cancer. They are:

• Change in the size, color, or shape of a wart or mole
• A sore that does not heal
• Persistent cough, hoarseness, or sore throat
• A lump or thickening in the breast or elsewhere
• Unusual bleeding or discharge (release of fluids)
• Chronic indigestion or difficulty in swallowing
• Any change in bowel or bladder habits

Diseases other than cancer can also produce these symptoms, so the symptoms need to be checked as soon as possible. Many forms of cancer have no early warning signs at all. For that reason, regular medical tests may be important. For example, women should check their own breasts regularly and should have regular mammograms (X rays of the breasts).

DIAGNOSIS

The first steps in diagnosing cancer are doing a complete physical examination and getting a medical history. During the physical examination, the doctor looks at, feels, and palpates (applies pressure by touch) various parts of the body. He or she watches for unusual size, feel, or texture of organs or tissues.

Some of the specific symptoms a doctor looks for during such a physical examination are the following:

• Thickening or sores in the lips, tongues, gums, throat, or roof of the mouth
• Tenderness or lumps in the neck
• Swelling or soreness of the lymph nodes in the neck, under the arms, and in the groin
• Sores, itchiness, or bleeding on the skin
• Sores or abnormal discharge from the ovaries, vagina, cervix, or uterus
• Discharge, unevenness, or discoloration of the breasts

• The presence of lumps or unusual masses in the breasts (in women) or in the rectum or testicles (in men)

If the doctor finds any of these signs, he or she may order tests. Some of the most common tests are the following:

• Sputum (material coughed up from the lungs; pronounced SPYOO-tum) is studied under a microscope to look for lung cancer.
• Blood tests can be used to look for tumor markers. A tumor marker is a special type of protein released by cancer cells. Blood tests are also used to follow the course of cancer and to see how well treatment is working.
• Imaging tests help doctors find tumors deep within the body. Most imaging tests use a form of radiation (such as X rays) to look for abnormal masses inside the body.
• A biopsy is the most reliable test for cancer. In a biopsy, the doctor removes a piece of tissue from an abnormal area of the body. The tissue is then studied under a microscope. A specialist can tell whether the tissue is normal or cancerous.

Screening tests are often helpful in detecting cancer at its earliest stages. A screening test is a relatively simple test that should be done regularly. A routine chest X ray is an example of a screening test. Some of the screening tests used for cancer include sigmoidoscopy (pronounced sig-moy-des-ca-pee; inspection of the colon) for colorectal cancer (see colorectal cancer entry), mammography for breast cancer, and a pap smear for cervical cancer.

Genetic testing is a relatively new form of screening that holds great promise. It can help doctors decide when people may be at risk for certain kinds of cancer because of their genetic makeup.

A TEAM EFFORT

Cancer treatment often requires the work of a team of doctors. At the head of the team is often an oncologist (pronounced on-KOLL-o-jist), a doctor who specializes in cancer care. Other doctors who may work with the oncologist include the following:

• Radiation oncologists, who specialize in the use of radiation to treat cancer.
• Gynecologist-oncologists who specialize in treatment of women with cancer of the reproductive organs.
• Pediatric-oncologists who specialize in the treatment of children with cancer.
• Radiologists, who use techniques such as X rays, ultrasound, and computed tomography (CT) scans to diagnose cancer.
• Hematologists, who study blood disorders.
• Pathologists, who analyze and identify the abnormal tissues that are present in tumors.

TREATMENT

Cancer treatment has two goals. First, as much of the original tumor as possible should be removed. Second, the tumor should be prevented from recurring or spreading to other parts of the body. One decision that often has to be made concerns the side effects of cancer treatments. Most cancer treatments are designed to kill cancer cells, but those treatments can also kill healthy cells. A patient undergoing cancer treatment can, therefore, become very ill from the treatments themselves.

In such cases, patients sometimes choose not to make use of treatments that try to cure the cancer. Instead, they are given other kinds of treatments designed to relieve their symptoms and make them more comfortable.

Many forms of cancer treatment are available. The form used with any one patient depends on many factors, including the patient's age, sex, general health, personal preferences, type and location of the cancer, and extent to which it has already metastasized (spread to other parts of the body, pronounced muh-TASS-tuh-sized). The major types of cancer treatment are surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone marrow transplantation.

Surgery

Surgery involves the removal of a visible tumor and is the most common form of cancer treatment. Surgery is most effective when the tumor is small and confined to one area of the body. Surgery can be used for many purposes:

• Treatment. When a tumor is removed surgically, a small amount of surrounding tissue is also removed. This ensures that no cancer cells are left in the area. Since cancer cells are often spread by means of the lymphatic system, nearby lymph nodes may also be removed.
• Cytoreduction. In some cases, it may be impossible to completely remove all the cancer cells by surgery. Cytoreduction ("cell reduction"; pronounced SITE-o-ree-duk-shun) involves the removal of as much cancerous tissue as possible. Any remaining abnormal tissue is then treated with radiation, chemotherapy, or both.
• Palliation. Tumors are sometimes so large that they cannot be removed completely by surgery. In such cases, palliative surgery is used to take out as much of the tumor as possible. This procedure often helps to relieve the symptoms of cancer even if it does not cure the disease itself. For example, a large tumor in the abdomen may press on and block a part of the intestine. The patient may be unable to digest food and feel constant pain and discomfort. Even if the whole tumor cannot be removed, some part of it can probably be taken out. The digestive system can then function normally again.
• Prevention. Preventive surgery may be used even if no tumors exist. The presence of abnormal tissue may suggest that tumors could eventually form. To avoid that possibility, the tissue can be removed. Preventive surgery is often used, for example, to prevent ulcerative colitis (see ulcerative colitis entry). About 40 percent of the people with this form of cancer die from the disease. People with the disease may choose to have their colons removed rather than risk dying of ulcerative colitis.
• Diagnosis. Whenever possible, biopsies are conducted with a needle. The needle is used to take out a small piece of tissue for study. Sometimes, a needle biopsy cannot be used. In those cases, surgery may be necessary to get the tissue needed for study.

Radiation

Radiation kills cancer cells. It can be used alone when a tumor cannot be removed surgically. More often, radiation is used in combination with surgery and chemotherapy. Radiation can be performed from either the outside or the inside of the body. An example of outside radiation is the use of X rays to treat a tumor. Inside radiation can be carried out by inserting pellets or liquids in a patient's body. Radiation given off by the pellets or liquid attacks and kills cancer cells.

Chemotherapy

Chemotherapy is the use of chemicals or drugs to kill cancer cells. It is used to destroy cells that have spread from the original tumor and are circulating in the body. The drugs used for chemotherapy can be given orally (by mouth) or by injection. They are used alone or in combination with surgery and radiation.

Chemotherapy is sometimes used before surgery or radiation because drugs are often able to kill cancer cells and reduce the size of a tumor. Surgery and radiation are likely to be more effective when used on smaller tumors. More often, chemotherapy is used after surgery or radiation treatments. In such cases, drugs may be able to destroy cancer cells remaining in the body after the initial treatment.

Immunotherapy

Immunotherapy is a relatively new form of cancer treatment. Its goal is to kill cancer cells by using chemicals that occur naturally in the body. Chemicals known as interferons are an example. Interferon can be given to a cancer patient to stimulate his or her own immune system to fight cancer more effectively.

Research is also being done to develop a cancer vaccine. A cancer vaccine is different from other kinds of vaccines. It is not being designed to prevent cancer. Instead, it will be given to patients who already have the disease. It is intended to help the patient's immune system fight cancer cells.

Hormone Treatment

Some forms of cancer grow faster when certain hormones are present. Examples of such cancers include cancer of the breast, prostate, and uterus. Hormone therapy involves the use of drugs that reduce the amount of hormones produced and their ability to cause changes in the body. These drugs can slow down the rate at which hormone-related cancers develop, extending the patient's life by months or years.

Bone Marrow Transplantation

Bone marrow is tissue found in the center of bones. It produces cells that develop into new blood cells. Radiation and chemotherapy often destroy bone marrow and the patient's body is no longer able to produce the amount of blood it needs to stay healthy.

Bone marrow transplantation involves the removal of some bone marrow from one person so that it can be given to another person. For the procedure to be successful, the two people must be closely related or have similar blood characteristics. Bone marrow transplantation can be important with patients who require very aggressive (serious) forms of treatment that are likely to destroy their own bone marrow.

Alternative Treatment

Many alternative forms of cancer treatment are available, however, patients should always seek the advice of trained health practitioners before trying alternative treatments. Treatment methods from other cultures can sometimes be effective in treating the symptoms of cancer or the side effects of radiation or chemotherapy. Two examples are acupuncture (a Chinese therapy technique where fine needles puncture the body) and Chinese herbal medicines. Body massage can help to ease muscle tension and reduce side effects such as nausea and vomiting.

Experts now believe that certain kinds of food, such as fruits, vegetables, and grains, can help protect against various forms of cancer. For example, a diet rich in fiber, which includes fruits and vegetables, seems to reduce the risk of colon cancer. Exercise and a diet low in fat can help control weight and reduce the risk of breast and colon cancers.

Scientists are not sure what is in foods that prevents cancer. Vitamins A, C, and E and the compound known as beta-carotene are likely prospects. So are two groups of compounds known as the isothiocyanates (pronounced I-so-THI-o-si-uh-nates) and the dithiolthiones (pronounced di-THI-ul-THI-ownz). These compounds are found in broccoli, cauliflower, cabbage, and carrots.

Some drugs used for cancer treatment may also help prevent the disease. Tamoxifen (pronounced tuh-MOK-sih-fen, trade name Nolvadex) is an example. Research is now being conducted to determine its effectiveness in preventing breast cancer. Compounds known as retinoids, obtained from vitamin A, are also being tested for use against head and neck cancers. The mineral selenium may also hold some promise for the prevention of some forms of cancer.

PROGNOSIS

"Lifetime risk" is the term used by cancer researchers to estimate the chance that a person will develop or die from cancer. In the United States, men have a 1 in 2 lifetime risk of developing cancer. For women, the risk is 1 in 3. African Americans have a higher lifetime risk than whites; they are also 30 percent more likely to die of cancer.

Most cancers can be cured if they are discovered and treated at an early stage. Prognosis depends on a number of factors, including the type of cancer, the stage at which it was detected, and how far it has already progressed. Personal factors, such as age, general health status, and treatment effectiveness also determine prognosis.

PREVENTION

Experts believe that the risk of getting cancer can be reduced by following some simple guidelines:

• Eat plenty of vegetables and fruits.
• Exercise vigorously for at least twenty minutes each day.
• Avoid excessive weight gain.
• Avoid tobacco, including secondhand smoke.
• Decrease or avoid consumption of animal fats and red meat.
• Avoid excessive amounts of alcohol.
• Avoid overexposure to sunlight.
• Avoid risky sexual practices.
• Avoid known carcinogens in the environment and workplace.

See also: Breast cancer, colorectal cancer, Hodgkin's disease, lung cancer, prostate cancer, and skin cancer.

FOR MORE INFORMATION

Books

Buckman, Robert. What You Really Need to Know about Cancer: A Comprehensive Guide for Patients and Their Families. Baltimore: Johns Hopkins University Press, 1997.

Dollinger, Malin. Everyone's Guide to Cancer Therapy. Toronto: Somerville House Publishing, 1994.

Morra, Marion E. Choices. New York: Avon Books, 1994.

Murphy, Gerald P. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment and Recovery. Atlanta, GA: American Cancer Society, 1997.

Periodicals

"What You Need to Know about Cancer." Scientific American (September 1996).

Organizations

American Cancer Society. 1599 Clifton Road NE, Atlanta, GA 30329. (800) 227–2345. http://www.cancer.org.

Cancer Care, Inc. 1180 Avenue of the Americas. New York, NY 10036. (800) 813–HOPE. http://www.cancercareinc.org.

Cancer Research Institute. 681 Fifth Avenue, New York, NY 10022. (800) 992–2623. http://www.cancerresearch.org.

National Cancer Institute. 31 Center Drive, Bethesda, MD 20892–2580. (800) 4–CANCER. http://www.nci.nih.gov.

National Coalition for Cancer Survivorship. 1010 Wayne Avenue, 5th Floor, Silver Springs, MD 20910. (301) 650–8868.

Web sites

Oncolink. [Online] University of Pennsylvania Cancer Center. http://cancer.med.upenn.edu. (accessed on October 13, 1999).

Cancer [Lat.,=the crab], in astronomy, constellation lying on the ecliptic (the sun's apparent path through the heavens) between Gemini and Leo; it is a constellation of the zodiac . It contains the star cluster Praesepe , but no bright stars. The tropic of Cancer takes its name from this constellation, in which the summer solstice was located about 2,000 years ago. Now, because of the precession of the equinoxes , the summer solstice has moved westward into the constellation Gemini. Cancer reaches its highest point in the evening sky in March.

cancer in medicine, common term for neoplasms, or tumors, that are malignant. Like benign tumors, malignant tumors do not respond to body mechanisms that limit cell growth. Unlike benign tumors, malignant tumors consist of undifferentiated, or unspecialized, cells that show an atypical cell structure and do not function like the normal cells from the organ from which they derive. Cancer cells, unlike normal cells, lack contact inhibition; cancer cells growing in laboratory tissue culture do not stop growing when they touch each other on a glass or other solid surface but grow in masses several layers deep.

Loss of contact inhibition accounts for two other characteristics of cancer cells: invasiveness of surrounding tissues, and metastasis, or spreading via the lymph system or blood to other tissues and organs. Whereas normal cells have a limited lifespan controlled by the telomere gene, which signals the end of the cell line, cancer cells contain telomerase, an enzyme that alters the telomere gene and allows the cell to continue to divide. Cancer tissue, growing without limits, competes with normal tissue for nutrients, eventually killing normal cells by nutritional deprivation. Cancerous tissue can also cause secondary effects, in which the expanding malignant growth puts pressure on surrounding tissue or organs or the cancer cells metastasize and invade other organs.

Virtually all organs and tissues are susceptible to cancer. Cancers are usually named for their site of origin. Cancer cells that spread to other organs are similar to those of the original tumor, therefore these secondary (metastatic) cancers are still named for their primary site even though they may have invaded a different organ. For example, lung cancer that has spread to the brain is called metastatic lung cancer, rather than brain cancer. Carcinoma in situ refers to a cancer that has not spread. (See neoplasm for more on cancer nomenclature.)

Cancer is the second leading cause of death in the United States. Lung cancer is the leading cause of cancer death in adults; leukemia is the most common cancer in children. Other common types of cancer include breast cancer (in women), prostate cancer (in men), and colon cancer (see also Hodgkin's disease ). The incidence of particular cancers varies around the world and sometimes according to ethnic group. For instance, African Americans have comparatively higher cancer rates and cancer mortality rates. It is unclear whether this is due to differences in exposure or to biological susceptibility. The number of diagnosed cases of cancer rose steadily in the United States for decades, but in 1998 it was announced that the number of new cases had begun to decline.

Causes of Cancer

Cancer results from mutations of certain genes that allow the cells to begin their uncontrolled growth. These mutations are either inherited or acquired. Acquired mutations are caused by repeated insults from triggers (e.g., cigarette smoke or ultraviolet rays) referred to as carcinogens. There is usually a latency period of years or decades between exposure to a carcinogen and the appearance of cancer. This, combined with the individual nature of susceptibility to cancer, makes it very difficult to establish a cause for many cancers.

The most significant avoidable carcinogens are the chemical components of tobacco smoke (see smoking ). Dietary components, like excessive consumption of alcohol or of foods high in fat and low in fiber rather than fruits and vegetables that contain antioxidants and necessary micronutrients, have also been linked with various cancers. Some cancers may be triggered by hormone imbalances. For example, some daughters of mothers who had been given DES (diethylstilbestrol) during pregnancy to prevent miscarriage developed vaginal adenocarcinomas as young women. Aflatoxins are natural mold byproducts that can cause cancer of the liver.

Certain carcinogens present occupational hazards. For example, in the asbestos industry, workers have a high probability of developing lung and colon cancer or a particularly virulent cancer of the mesothelium (the lining of the chest and abdomen). Benzene and vinyl chloride are other known industrial carcinogens.

X rays and radioactive elements are also carcinogenic; the high incidence of leukemia and other cancers in Japanese survivors of the atomic bombing of Hiroshima and Nagasaki and the increased incidence of thyroid cancer after the Chernobyl nuclear disaster give evidence of this. Exposure to the ultraviolet radiation of sunlight is the leading cause of skin cancer .

Many other substances have been identified as carcinogenic to a greater or lesser extent, including chemicals in pesticides that leave residues on foods. The Delaney clause, an amendment (1958) to the U.S. Food, Drug, and Cosmetic Act that prohibits even minuscule amounts of carcinogens in the food supply, has provided the impetus for the investigation of many such chemicals but has also been a source of controversy between industry and environmentalists.

In the early 20th cent., the American virologist Peyton Rous showed that certain sarcomas affecting fowl could be transmitted by injection of an agent invisible under the microscope and later indentified as an RNA-containing virus. Other research uncovered oncogenic, or tumor-causing, viruses, first in experimental animals and then in humans. The Epstein-Barr virus , a member of the herpesvirus group, has been linked with a number of human cancers, including the lymphomas that often occur in immunosuppressed people, such as people with AIDS . Several human papillomaviruses (HPV) have also been shown to initiate cancers. For example, some types of HPV cause genital warts known as condylomata acuminata, which can lead to invasive cancer of the cervix, vulva, vagina, or penis, and another human papillomavirus has been associated with some forms of Kaposi's sarcoma . In addition, hepatitis B has been shown to increase the risk of liver cancer. Bacteria have also been associated with cancer. For example, the Helicobacter pylori bacterium that causes many ulcers is also associated with an increased risk of stomach cancer.

Cancer Susceptibility

Risk to humans from carcinogens depends upon the dose and a person's biologic susceptibility. Factors influencing a person's biological susceptibility to cancer include age, sex, immune status, nutritional status, genetics, and ethnicity. Only 5% of all cancers in the United States are thought to be explained by inherited genetic mutations. Known genes associated with hereditary cancer include the aberrant BRCA1 and BRCA2 genes that increase breast cancer risk and the HNPCC gene that is linked with colon cancer. In hereditary forms, it is often the normal gene of the allele that is injured or destroyed, leaving the abnormal inherited gene in control. Nonhereditary cancers sometimes involve the same gene mutations that hereditary forms have.

Tumor Development

Most bodily insults by carcinogens come to nothing because DNA has built-in repair mechanisms, but repeated insults can eventually result in mutations or altered gene expression in key genes called oncogenes and tumor-suppressor genes. Oncogenes produce growth factors, substances that signal a cell to grow and divide into daughter cells; tumor-suppressor genes (such as the p16, p53, and BRCA1 genes) normally produce a negative growth factor that tells a cell when to stop dividing. The abnormally inactivated tumor-suppressor gene or the abnormally activated oncogene is inherited by each of the cell's daughter cells, and a tumor develops. In many cases tumors remain small and in one place ( in situ ) for years, but some develop their own blood vessels (a process known as angiogenesis) and begin to grow and spread.

Symptoms

The classic symptoms of cancer are rapid weight loss; a change in a wart or mole; a sore that does not heal; difficulty swallowing; chronic hoarseness, blood in phlegm, urine, or stool (a consequence of angiogenesis); chronic abdominal pain; a change in size or shape of the testes; a change in bowel habits; a lump in the breast; and unusual vaginal bleeding. Many of these and other symptoms are often nonspecific, e.g., weakness, loss of appetite, and weight loss, and thus are not obvious in the early stages. Sometimes the side effects of tumor growth are more severe than the actual effects of the malignancy; for example, some tumors secrete materials such as serotonin and histamine that can cause drastic vascular changes. Conversely, cancers that destroy tissue may also have serious effects, e.g., malignant destruction of bone tissue may raise the blood level of calcium.

Prevention and Detection

As more has been learned about cancer, emphasis on prevention and early detection has increased. Cessation of smoking and other tobacco use is the most important controllable means of prevention; smoking causes about 30% of the cancer deaths in the United States. A diet low in fat and high in fiber, including a variety of fruits and vegetables (especially those high in antioxidants), is also recommended. Effective protection against the rays of the sun is recommended to avoid skin cancer. Another preventive approach is vaccination against cancer-causing viruses, such as the hepatitis B virus.

Cancers caught early, before metastasis, have the best cure rates. A number of screening tools are now available to allow early detection and treatment. Among these are monthly breast self-examinations and regular mammography and Pap tests for women, regular self-examination of the testes for young men, and, for older men, regular examination of the prostate gland with blood tests for prostate-specific antigen (PSA) tumor marker (a substance in the body that heralds an increased cancer risk). Colonoscopy plus physical examination and laboratory tests for carcinoembryonic antigen (CEA) are recommended for detection of colon cancer. Self-examination of the skin is important for the early detection of skin cancers. Suspicion of a tumor may be confirmed by X-ray study, endoscopy (see endoscope ), blood tests for various tumor markers, and biopsy from which the cells are examined by a pathologist for malignancy.

Treatment

Developments in the treatment of cancer have led to greatly improved survival and quality of life for cancer patients in the past three decades. Traditionally, cancer has been treated by surgery, chemotherapy, and radiation therapy. In recent years immunotherapy has been added to that list. New drugs and techniques are constantly being researched and developed, such as antiangiogenic agents (e.g., angiostatin and endostatin), genetically engineered monoclonal antibodies , retinoid agents, and therapeutic vaccines (agents that stimulate the immune system to attack cancerous cells).

For most kinds of cancer, surgery remains the primary treatment. It is most effective if the cancer is caught while still localized. Some cancers that spread to the lymph system are sometimes treated by extensive surgical removal of tissue, but the trend is toward more conservative procedures (see mastectomy ). Cryosurgery, the use of extreme cold, and electrodessication, the use of extreme heat, are also being used to kill cancerous tissue and the surrounding blood supply. If the cancer has metastasized, surgery is often replaced by or followed by radiation therapy (which is a localized therapy) and chemotherapy (which is a system-wide therapy).

For some cancers, radiation therapy—either from an external beam or from implanted radioactive pellets—is the primary treatment. The usual forms are X rays and gamma rays. Use of radioactive elements specific for particular target organs, such as radioactive iodine specific for the thyroid gland, is effective in treating malignancies of those organs.

Cytotoxic chemotherapy is used as a primary treatment for some cancers, such as lymphomas and leukemias or as an addition to surgery or radiation therapy. Cytotoxic drugs (drugs that are toxic to cells) are aimed at rapidly proliferating cells and interfere with nucleic acid and protein synthesis in the cancer cell, but they are often toxic to normal rapidly proliferating cells, such as bone marrow and hair cells. Often a combination of cytotoxic drugs is used. Drugs that reduce side effects may be added to the treatment, such as antinausea agents.

Hormonal chemotherapy is based upon the fact that the growth of some malignant tumors (specifically those of the reproductive organs) is influenced by reproductive hormones. Tamoxifen is a naturally occurring estrogen inhibitor used to prevent breast cancer recurrences. Flutamide is sometimes used in prostate cancer to inhibit androgen uptake. Sex-hormone related drugs such as DES and tamoxifen, which may be carcinogenic under some conditions, have proven to be protective under others.

More specifically targeted drug therapies have begun to be explored as a better understanding of the molecular biology of individual cancers has been developed. Such drugs are designed to kill only cancer cells while having fewer side effects. Gleevec (STI-571), which is used to treat chronic myelogenous leukemia and some other cancers, inhibits certain kinase receptors that become hyperactive in cancer cells, resulting in the cells' rapid reproduction.

Immunotherapy (sometimes called biological therapy) uses substances that help the body mobilize its immune defenses. Some attack the tumor itself, while others bolster the body's ability to withstand conventional chemotherapy treatment. Other new or experimental therapies include drugs that inhibit angiogenesis and photodynamic therapy, in which a patient is given a drug to make the tumor light-sensitive, after which the tumor is exposed to bright laser light. The best choice of treatment will increasingly be influenced by the growing field of molecular pathology, in which characteristics of individual cancers (e.g., virulence or resistance to a particular treatment) can be revealed by analysis of their genetic characteristics rather than by the microscope.

Besides treatment of the cancer itself, progress has been made in the management of the chronic pain that often accompanies cancer and in the education of patients and physicians in such techniques as biofeedback, acupuncture, and meditation and the appropriate use of narcotics and other medications. Because of improvements in early detection and treatment, many more people are now living with cancer. Over half of all people with cancer now survive for five or more years.

Bibliography

See C. N. Coleman, Understanding Cancer (1998); A. H. Ko et al., Everyone's Guide to Cancer Therapy (rev 5th ed. 2008); S. Mukherjee, The Emperor of All Maladies (2010). See also publications of the National Cancer Institute and the American Cancer Society.

Cancer

An Ancient Affliction

What is Cancer?

How Does Cancer Begin?

How Does Cancer Spread?

What Causes Cancer?

How Do People Know They Have Cancer?

How is Cancer Diagnosed and Treated?

Will There Ever Be a Cure for All Cancers?

Can Cancer Be Prevented?

Living with Cancer

Resources

Cancer is a group of many related diseases in which abnormal celh grow out of control and spread.

KEYWORDS

for searching the Internet and other reference sources

Carcinogens

Carcinoma

Metastasis

Oncogenes

Oncology

Osteosarcoma

An Ancient Affliction

The disease we call cancer has been around as long as we have. Evidence of cancerous growths, or tumors, has been found among fossilized bones and in human mummies dating from ancient Egypt. The ancient Greek physician Hippocrates (hi-POK-ra-tees) was the first to use the word “carcinoma” (kar-si-NO-ma) to describe various kinds of tumors. Hippocrates noted that parts sticking out from some tumors looked like the limbs of a crab. The word “cancer” comes from the Latin word for crab. In 1913, only one in nine people had a chance of being alive five years after a diagnosis of cancer. Today, depending on the cancer, more than 50 percent of people with cancer will survive the disease. For many types of cancer, early detection and treatment result in a normal lifespan.

What is Cancer?

In all forms of cancer, cells grow out of control and may spread. In the United States, half of all men and one third of all women will develop one type of cancer or another during their lifetime. Almost everyone knows someone who has had cancer, and it is natural for children to worry that they might get it. But cancer in children is very rare. Some cancers are more common than others. The cancers that adults get most frequently are cancers of the skin, lungs, and colon and rectum. Breast cancer is a common cancer among women. Childhood cancers include leukemia (loo-KEE-mee-ya), lymphoma (lim-FO-ma), brain cancer, and osteosarcoma (os-tee-o-sar-KOME-a) (bone cancer). Cancer is sometimes referred to as a malignancy or a malignant tumor.

How Does Cancer Begin?

With more than 100 types of cancer, the disease can arise in almost any part of the body. Each cancer is different, but they all start the same way. A healthy body is home to more than 10 trillion cells (at least 100 times as many stars as there are in the entire Milky Way galaxy). Just as neighbors cooperate to maintain an orderly community, cells usually grow, divide, and die in a controlled fashion. But cancer cells are renegades, bad neighbors in the cellular community. Cancer begins when a single cell starts to multiply inappropriately.

What turns a good cell bad? The operating instructions for every-thing that our cells do are contained in the genes, packets of information that we inherit from our parents. Genes are made of a substance called DNA. The function of genes is to make proteins, the building blocks of life that carry out the work of the genes. When a gene inside a cell is switched on, the cell starts producing the required protein. Sometimes genes become altered, and we say they have mutated. Mutations in a gene can affect how the gene works; for example, a mutated gene might produce too much of a protein, or perhaps none at all.

Life proceeds by cell growth and division, and this process is directed by a collection of genes whose proteins work like traffic cops to encourage growth, or to halt it. When these genes become mutated, the proteins they make may erroneously tell cells to continue growing, like a traffic light stuck on green. The mutated genes are called oncogenes. Normal cells with damaged DNA die. But cancer cells with damaged DNA may not.

Many tumors need 30 to 40 years to develop, which explains why children rarely get cancer. But it is possible for a person to inherit a mutant cancer-causing gene. When that happens, people sometimes get cancer at an earlier age.

Genes can undergo mutations as a result of cancer-causing substances called carcinogens (kar-SIN-o-jens) in the environment as well as chemicals in our own cells. Another source of mutations is copying mistakes that occur when DNA is replicated during cell division. Cells normally have repair systems to correct such errors. But when the repair system slips up, the damage becomes a permanent part of that cell and of the cell’s descendants. If a person has a faulty repair system, mutations in the genes will build up rapidly, making the cells more likely to become cancerous. Faulty repair plays a role in certain kinds of colon, skin, and breast cancers.

The body’s defenses are impressive, and it is difficult for cancer to get started. But imagine that a renegade cell has managed to evade every one of the cell’s checkpoints and has formed a tumor. Now what? To grow larger than a millimeter (about the size of a pinhead), a tumor needs a blood supply, so it sends out a chemical signal to cause blood vessels to grow.

The U.S. and the World

• The U.S. National Cancer Institute says that 8.4 million people—about 3 percent of the population in 1999— have a history of cancer. The death rates for most major cancers have declined since the 1970s, because of earlier detection and better treatment. About 2 million women are breast cancer survivors and 1 million men are prostate cancer survivors.
• Still, cancers killed 539,577 Americans in 1997. This accounted for 23 percent of all deaths thatyear, making cancer the second leading cause of death after heart disease. Lung cancer caused the majority of the cancer deaths (29 percent), followed by stomach cancer (23.5 percent).
• Each year, about 150 of every 1 million Americans under age 20 will be diagnosed with cancer. But the chances for surviving at least five years with cancer increased for children between the early 1980s (64 percent survived) and the early 1990s (74 percent). That is better than the five-year survival rate for all cancers, which was about 60 percent in the 1990s.
• Worldwide, cancer caused an estimated 7.2 million deaths in 1998, which accounts for 13 percent of all deaths. Lung cancer was the leading cause, accounting for 17 percent of all cancer deaths.
• Cancer deaths worldwide have increased slightly since 1993, when about 6 million people died of cancer. That represented 12 percent of all deaths worldwide in 1993.
• About 81 million people worldwide were living with cancer in 1998. The World Health Organization (WHO) expects the prevalence of cancer cases to increase in the first 25 years of the twenty-first century in developing nations.
• The World Health Organization estimates about 15 million new cases of cancer will develop in the year 2020, compared with 10 million new cases a year in the late 1990s. Reasons include increased smoking in developing nations, unhealthy diets, and more people living to old age, when cancer risk is higher.
• The World Health Organization estimated in the mid-1990s that 15 percent of all cancers worldwide could be prevented by controlling infections. For example, more than 400,000 cases of liver cancer were tied to infection with hepatitis in the mid-1990s. Parasites in food also can lead to stomach cancers.
• Other trends to watch between 1999 and 2025, according to WHO: Lung cancer and colorectal cancer cases and deaths will increase, largely because of increased smoking and unhealthy diet. Women will die in higher numbers from lung cancer in almost all industrialized countries. Stomach cancer is expected to become less common, because of improved food conservation, changes in diet, and declining infection. Cervical cancer is predicted to decrease in industrialized countries because of increased screening and it might decrease in the developed world if a vaccine is developed. And, finally, liver cancer will decrease as the rates of immunization and screenings for hepatitis increase.

How Does Cancer Spread?

Normal cells do not wander. But some types of cancer cells do, which is what makes them so dangerous. The process is called metastasis (meh-TAS-ta-sis). Although it may be fairly easy to remove the main, or primary, tumor in cancer, metastasis cannot usually be cured by surgery alone.

In order for cancer to spread to other parts of the body, it must detach from its original location, invade a blood vessel, travel through the circulation to a far-away site, and set up a new cellular colony. At every one of these steps, it must outsmart the many controls the body has to keep cells where they belong.

New techniques show that abnormal cells from a tumor often are circulating even when doctors can find no evidence of spread. We call this undetectable spread micrometastasis (MY-kro-meh-TAS-ta-sis). Once a cancer cell has found a new home, it must reverse all the steps it took in liberating itself. It has to attach to the inner lining of a blood vessel, cross through it, invade the tissue beyond, and multiply. Probably fewer than 1 in 1,000,000 of the cancer cells that make it into the bloodstream survive to take up residence elsewhere.

Cancer cells “prefer” small blood vessels, and the first small blood vessels a freed cancer cell encounters are those of the lungs. So the lungs are the most common site of spread for cancer, followed by the liver. Much of how cancer spreads is still a mystery. Some tissues—for example, cartilage and brain tissue—seem more resistant to cancer. And some animals almost never have cancer.

What Causes Cancer?

A risk factor is anything that increases a person’s chance of getting a disease. But having a risk factor does not mean that a person will get the disease for sure. People get cancer as a result of a complex set of interactions between their genes and the environment. We are just beginning to understand these reactions.

Tobacco

Tobacco is a lethal cancer-causing substance. It causes 30 percent of total cancer deaths every year in the United States, affecting the lungs and other organs of the body. Almost all lung cancer is the result of smoking. The younger a person starts to smoke, the greater the risk of cancer.

Food and alcohol

In the United States, diet has been associated with certain cancers, particularly diets containing high amounts of animal (saturated) fat and red meat. After years of studies, coffee has not been proved to cause cancer, nor have artificial sweeteners. Eating insufficient quantities of fruits and vegetables appears to contribute to cancer, for reasons no one understands. It may be that fruits and vegetables help to block the cancer-causing effects of our own bodies. Drinking large amounts of alcohol increases the risk of cancer of the upper respiratory and digestive tracts, and alcoholic liver disease can lead to liver cancer. Even moderate drinking may contribute to breast and colon and rectal cancer.

Radiation

Some forms of radiation cause cancer. But most cancer deaths from radiation are caused by natural sources such as the sun’s ultraviolet rays. For example, sunburns during childhood are a key factor in causing a kind of skin cancer called melanoma (mel-a-NO-ma). But electric power lines, household appliances, and cellular telephones have so far not been proven to cause cancer. Radiation from nuclear materials and reactions does cause cancer, but most people are not exposed to levels high enough to harm them.

Chemicals

In the past, some people who worked with certain chemical substances such as asbestos (az-BES-tos) and benzene (BEN-zeen) had a greater chance of getting lung cancers and other kinds of cancers. But strict government regulations have limited the use of these substances and sharply reduced the numbers of these cancers.

How Do People Know They Have Cancer?

Many symptoms of cancer such as weight loss, fever, fatigue, and various kinds of lumps could also be caused by other diseases. Some cancers may cause no symptoms until they have spread. Based on the most commonly occurring cancers, the American Cancer Society publishes a list

American Cancer Society

The American Society for the Control of Cancer (ASCC) was founded in 1911 to educate the public about the dangers of cancer. In 1943, Mary Lasker, the wife of an advertising tycoon who himself would die of cancer, walked into the office of Clarence C. Little, the managing director of the ASCC, and asked him how much money the society was spending on research. Nothing, Little told her.

Lasker immediately began a campaign to raise funds for the renamed American Cancer Society (ACS). A granting program was begun in 1946. By 1948, the ACS had raised around $14 million. Today, the ACS has chartered divisions throughout the country and over 3,400 local units. ACS is the largest source of private, not-for-profit research funds in the United States, second only to the federal government in total dollars spent.

of seven warning signs of cancer. These symptoms do not mean that a person has cancer, but if they occur, a person should see the doctor:

Change in bowel or bladder habits (for instance diarrhea that does not go away or pain on urination)

A sore anywhere on the skin that does not heal

Unusual bleeding or discharge from the nose, mouth, skin, nipple, or vagina

A thickening or lump in the breast or elsewhere

Indigestion or difficulty in swallowing

Obvious changes in a wart or mole

Nagging cough, particularly if these symptoms occur in a cigarette smoker.

Eating for Health

The American Cancer Society recommends the following general nutritional guidelines to help people stay healthy:

• Choosing most foods from plant sources such as vegetables, fruits, and grains
• Limiting intake of high-fat foods, especially from animal sources
• Staying physically active
• Maintaining a healthy weight
• Limiting consumption of alcoholic beverages

How is Cancer Diagnosed and Treated?

Diagnosis

Diagnosing cancer involves removing some tissue for evaluation. This procedure is called a biopsy (BY-op-see). Once the diagnosis is made, a treatment plan is put together. To do that, it is necessary to determine how widespread the disease is, and how serious. “Staging” the disease means assigning letters and numbers to it as a way of indicating whether it has spread and how far. There are several systems for staging, depending on the type of cancer. Generally speaking, the smaller the tumor, the more curable it is, although some cancer can be unpredictable. The outlook for some cancers, for example, leukemia and lymphoma, is judged according to other criteria. Cancer is classified by the part of the body in which it began and by how it looks under a microscope.

Treatment

Treatment for cancer includes surgery, radiation, and chemotherapy (kee-mo-THER-a-pee), alone or together. Because different types of cancer vary in how fast they grow, where they spread, and how they respond to treatment, treatment is specifically tailored to the kind of cancer a person has.

Surgery is the oldest form of treatment for cancer, and it still offers the greatest chance of cure for many kinds of cancer. About 60 percent of patients with cancer will have some type of surgery.

Radiation therapy uses high-energy particles or waves to damage cancer cells that surgery cannot catch because they are too small.

Chemotherapy uses anticancer drugs to treat cancer. Chemotherapy drugs are given through a vein (also called an intravenous or IV line) or by mouth as pills. These drugs enter the bloodstream and reach places in the body that surgery and radiation cannot reach. Chemotherapy is often given for cancer that has spread.

Another kind of therapy interferes with the production of substances in the blood called hormones (HOR-mones) that stimulate certain kinds of cells (for example, cells in the breast) to grow.

Will There Ever Be a Cure for All Cancers?

Every day researchers learn a little more about how the cell works, and many of these discoveries are being applied to cancer research. Many current therapies have side effects because they kill healthy cells as well as cancer cells or affect the function of other parts of the body. So one area of research scientists are working on is therapies that will kill only cancer cells and that will leave healthy cells alone. Another area of research is investigating ways of helping the body’s own defense system to fight cancer. Scientists are also exploring substances in food or drugs that will prevent cancer from developing in the first place.

Clinical Trials and New Cancer Treatments

Studies of new or experimental treatments in patients are known as clinical trials. Research in cancer could not move forward without them because drugs may work very differently in people than in the animals in which the drugs first proved successful.

Clinical trials seek to answer such questions as:

• Does this new treatment work?
• Does it work better than other treatments already available?
• Do the benefits outweigh the risks, including side effects?

Although there are risks to new treatments, clinical trials are done only when there is some reason to believe that the treatment will be of value to the patient.

Participating in a clinical trial is completely up to the patient. The doctor may suggest it, or patients can request information about clinical trials from the U.S. National Cancer Institute.

Can Cancer Be Prevented?

In the United States, 1.2 million people are diagnosed with cancer each year. There is no way to prevent cancers children get. But many cancers that occur in adults could be prevented by changes in a person’s lifestyle. For example, cancers caused by cigarette smoking and drinking a lot of alcohol could be prevented completely. Limiting certain kinds of foods, such as red meats and animal fats, and eating lots of fruits and legumes (such as peas and lentils) may help reduce the risk of getting many cancers. Physical activity helps to avoid obesity and may have other protective effects against cancer. Most of the one million skin cancers that are diagnosed each year could be avoided by staying out of the sun.

Regular cancer checks, called screenings, for cancer of the breast, colon, rectum, cervix, prostate, testes, mouth, and skin are an effective way of detecting cancer early enough to be treated successfully. In addition, self-examination for breast and skin cancers also helps to detect tumors at earlier stages. The American Cancer Society estimates that if all Americans participated in regular cancer screenings, survival would be dramatically improved.

Living with Cancer

A cancer diagnosis is usually shocking and frightening. A person’s life is suddenly disrupted by surgery, treatment, visits to the doctors, and changing personal relationships. Children with cancer may have to miss school for a time or to give up sports or other activities. A person may feel anger at themselves or others, or at God. Children especially may feel that something they did caused the cancer, especially if it is a brother or sister who is sick. Family, physician, friends and organizations, religious groups and clergy, and self-help groups all may be an important source of support. Each person’s way of dealing with cancer is unique. Even with cancers that will cause death, a person may live for many years. And more than 70 percent of children and adolescents with cancer are successfully treated.

Alternative and complementary therapies

Many patients seek out other kinds of therapies during their treatment. Cancer is a frightening word, and some people will do anything, no matter how unlikely to work. A number of alternative treatments are themselves dangerous, and can distract from effective treatment. Some can be costly as well. These therapies generally are of two kinds:

• Alternative therapies are often promoted in the mass media as cancer cures. Patients should be aware that these therapies have either not been tested for safety and effectiveness, or have been tested and found to be ineffective.
• Complementary therapies, on the other hand, are used in addition to standard therapy. They may help to relieve symptoms of the disease or side effects of treatment, or they just may make patients feel better. Examples of complementary therapies are meditation to relieve stress and peppermint tea to combat nausea (stomach upset) from chemotherapy.

Patients who are thinking of using alternative or complementary therapies should first discuss it with their health care team.

See also

Bladder Cancer

Brain Tumor

Breast Cancer

Colorectal Cancer

Hepatitis

Kidney Cancer

Leukemia

Lung Cancer

Mouth Cancer

Pancreatic Cancer

Polyps

Prostate Cancer

Stomach Cancer

Skin Cancer

Testicular Cancer

Tumor

Viral Infections

Resources

U.S. National Cancer Institute, Bethesda, MD 20892. The NCI coordinates the government’s cancer research program, and provides information about cancer to patients, their families, and the public. Its Cancer Information Service posts a What You Need to Know About Cancer series of fact sheets at its website, and its “kidscontents” fact sheet When Someone in Your Family Has Cancer can help with resources and referrals. Telephone 800-4-CANCER http://www.nci.nih.gov/wyntk_pubs/index.html http://rex.nci.nih.gov/NCI_Pub_Interface/guide_for_kids/kidscon-tents.html

American Cancer Society (ACS), 1599 Clifton Road NE, Atlanta GA 30329-4251. ACS is a national, not-for-profit society that provides upto-date health information about cancer. Telephone 800-ACS-2345 http://www.cancer.org

KidsHealth.org and the Nemours Foundation publish Childhood Cancer and What is Cancer and What Happens When Kids Get It?, offering practical, straightforward advice for parents and children on the kinds of cancer children get. http://www.KidsHealth.org

University of Pennsylvania Cancer Center. The OncoLink website at the University of Pennsylvania posts information about all aspects of cancer. http://www.cancer.med.upenn.edu

The World Health Organization posts information at its website about cancer and other noncommunicable diseases worldwide. http://www.who.org

cancer A wide variety of diseases characterized by uncontrolled growth of tissue. Dietary factors may be involved in the initiation of some forms of cancer, and a high‐fat diet has been especially implicated. There is some evidence that antioxidant nutrients such as carotene, vitamins C and E, and the mineral selenium may be protective. See also carcinogen.

Patients with advanced cancer are frequently malnourished, the condition of cachexia.

can·cer / ˈkansər/ • n. the disease caused by an uncontrolled division of abnormal cells in a part of the body. ∎  a malignant growth or tumor resulting from such a division of cells: skin cancers. ∎ fig. a practice or phenomenon perceived to be evil or destructive and hard to contain or eradicate. DERIVATIVES: can·cer·ous / ˈkansərəs/ adj.

Cancer (abbr. Cnc, gen. Cancri) The faintest constellation of the zodiac, in which the Sun lies for three weeks from late July until mid-August. Cancer represents a crab. Its brightest star, Beta Cancri, is magnitude 3.5; Zeta Cancri is a double star of magnitudes 5.1 and 6.2. The main feature of the constellation is the open star cluster M44, Praesepe. There is also a smaller 7th-magnitude star cluster, M67,½° wide.

Cancer Northern constellation between Gemini and Leo. It contains two open clusters: M44, the Praesepe or Beehive Nebula (NGC 2632), and M67 (NGC 2692). The brightest star is Beta Cancri.

cancer Group of diseases featuring the uncontrolled proliferation of cells (tumour formation). Malignant (cancerous) cells spread (metastasize) from their original site to other parts of the body. There are many different cancers. Known causative agents (carcinogens) include smoking, certain industrial chemicals, asbestos dust and radioactivity. Viruses are implicated in the causation of some cancers. Some people have a genetic tendency towards particular types of cancer. Treatments include surgery, chemotherapy with cell-destroying drugs and radiotherapy (or sometimes a combination of all three). Early diagnosis holds out the best chance of successful treatment.

cancer zodiacal constellation of the Crab XIV; malignant tumour XVII. — L. cancer crab, creeping ulcer, after Gr. karkínos crab, karkinōma CARCINOMA.

Cancer in astrology, the fourth sign of the zodiac, which the sun enters at the northern summer solstice (about 21 June).

cancer •amasser, gasser, macassar, Makassar, Mombasa, Nasser •relaxer, waxer •salsa •cancer, romancer •piazza • necromancer • madrasa •Kinshasa, Lhasa, passer, Tarrasa, Vaasa •advancer, answer, chancer, dancer, enhancer, lancer, prancer •tazza •addresser, aggressor, assessor, compressor, confessor, contessa, depressor, digresser, dresser, guesser, intercessor, lesser, Odessa, oppressor, possessor, professor, represser, successor, transgressor, Vanessa •Alexa, flexor, vexer •Elsa, Kielce •censer, censor, dispenser, fencer, Mensa, sensor, Spenser •seltzer •Faenza, Henze •indexer • hairdresser • predecessor •microprocessor, processor •acer, bracer, chaser, debaser, embracer, facer, macer, mesa, pacer, placer, racer, spacer, tracer •Ailsa • steeplechaser •greaser, Lisa, Nerissa, piecer, Raisa, releaser •pizza