Population Screening

As scientific research reveals more information about treating diseases and maintaining good health, it has become increasingly important to identify diseases in their early stages in order to treat them most effectively. Thus, researchers have developed tests for some diseases to identify people at high risk for the disease before the symptoms of the disease actually appear. These tests are routinely administered to individuals in a defined population who have no apparent symptoms of the disease being screened. This process is called population screening. A primary goal of population screening is to predict with high accuracy which individuals in this group are at significant risk of developing or transmitting a disease. Once individuals at high risk for a disease are identified, confirmatory (diagnostic) tests are then performed to detect the screened-for disease with greater certainty.

Screening versus Diagnostic Tests

Examples of routine population screening currently used in the health care field include Pap smears for women to predict their risk for cervical cancer, mammograms for women to predict their risk for breast cancer, the PPD skin test to predict exposure to tuberculosis mycobacterium (TB) in health care workers, and the prostatic antigen screening (PSA) test for men to predict their risk for prostate cancer.

However, screening tests have limits. A screening test only indicates who, in a given population, is most likely to be at higher risk for developing a disease. As a result, screening tests will have both false positives and false negatives. A false positive occurs when a test misidentifies individuals as being higher risk, when they are actually not at higher risk. A false negative occurs when individuals with a higher risk for the disorder are not identified by the screening test. For this reason, a diagnostic test is done following a positive screening test. A diagnostic test determines with relative certainty whether an individual has a disorder and thus rules out false positives. Diagnostic tests are typically more expensive and/or more invasive and therefore cannot be used as part of the screening process.

Criteria for a Screening Program

Despite limitations, population screening can still be very advantageous for improving public health. However, for population screening to be beneficial, a disease should meet several conditions. There should be a high rate of occurrence of the disorder or a significant number of individuals who carry the disease in the high-risk population; the disorder could potentially have a harmful impact on an individual's health, if not identified and treated; the disorder must be treated or prevented though not necessarily cured; testing should be minimally invasive, easily carried out, and relatively inexpensive; and the testing method must have been studied and scientifically demonstrated to be accurate, reliable, and confirmed by follow-up testing. In addition, testing should be performed only after informed consent is obtained from the individual or responsible party.

Screening for Inherited Disorders

The disorders that are screened for, above, may or may not be genetic. However, with the numerous advances in genetic research, public health concerns have shifted to include the growing number of recognized inherited disorders. Screening for inherited disorders began in the early 1960s, with testing for phenylketonuria (PKU), a metabolic disease that causes severe mental deficiency. Since that time, developments such as the completion of the Human Genome Project (HGP) has resulted in an increase in the number of genetic screening tests available. Types of population screening for inherited disorders can include newborn screening and carrier screening of individuals within populations known to be at high risk for certain inherited disorders.

Newborn Screening.

In the United States, every state requires that certain screening tests be done on all newborn infants. Interestingly, individual states vary significantly as to which screening tests they require. For instance, while it is mandatory to screen for PKU in every state, other relatively common inherited disorders, such as medium-chain acyl-CoA dehydrogenase deficiency and congenital adrenal hyperplasia, are only screened for in selected states. Furthermore, some private organizations offer an expanded selection of testing for genetic disorders in newborns beyond what individual states mandate.

Newborn screening is the only population-based type of screening for inherited disorders. One public health benefit of population-based screening means that everyone is tested. This is especially useful for studying inherited disorders, since it permits scientists to determine with great accuracy how frequently some inherited disorders occur in the general population.

In simple terms, there are two types of testing done for newborn screening: non-DNA-based testing and DNA-based testing. With DNA-based testing, an individual's DNA is tested directly. With non-DNA-based testing, two indirect methods are used: Enzymatic or electrophoretic testing methods are used to figure out whether an individual has an inherited disorder.

The most well-known newborn screening test is for PKU. PKU is an autosomal , recessively inherited metabolic disorder characterized by a lack or defect of phenylalanine hydroxylase, an enzyme involved in the metabolism of an amino acid called phenylalanine. Because this enzyme does not function properly, persons with PKU have a buildup of phenylalanine in their bodies, which results in severe mental retardation if untreated. Treatment currently involves dietary restriction of phenylalanine. Because phenylalanine is an essential amino acid (meaning that our bodies cannot make it, and it is essential for life), people with PKU cannot eliminate the substance entirely from their diet. Instead they must take care to modulate the amount they consume, because they cannot metabolize extra phenylalanine. Therefore, persons with PKU are usually under the care of a dietitian, who helps them to eat a balanced diet with the right amount of phenylalanine. Most importantly, by following the proper diet, individuals with PKU will not develop mental retardation.

Screening for PKU is done using the Guthrie test, a bacterial inhibition assay, a non-DNA-based (enzymatic) laboratory test. Another example of a non-DNA-based test is hemoglobin electrophoresis, which is done to determine the types of hemoglobin an individual carries. This information is a direct reflection of an individual's genetic makeup. Some other examples of disorders screened for, using non-DNA-based tests, include hypothyroidism, congenital adrenal hyperplasia and hemoglobinopathies (such as sickle cell disease and thalassemias). In contrast, DNA-based genetic testing is a relatively new clinical tool in newborn screening. In at least one state, DNA-based newborn screening is done for cystic fibrosis.

Carrier Testing.

In contrast to newborn screening, which is done on all newborns regardless of family history or ethnicity, carrier testing is aimed at a specific population that is viewed to be at high risk for a given disorder. In addition, carrier testing is always DNA-based, whereas newborn screening is typically non-DNA-based. Carrier testing is offered to determine if individuals carry a single non-working copy of a gene for a genetic disorder.

In general, individuals who carry one copy of a non-working gene will not have symptoms or signs of the disorder. When two individuals who are carriers for the same inherited disorder have a child, that child is at a 25 percent risk of inheriting a copy of the non-working gene from each parent, and will usually show symptoms and signs of the inherited disorder. Diseases that may be inherited in this way are called autosomal recessive disorders, and include sickle cell disease, Tay-Sachs disease, and cystic fibrosis.

In the late 1990s, a panel convened at the National Institutes of Health and recommended that carrier screening for cystic fibrosis be offered to a number of populations, including adults with a family history of the disease, the partners of people who had the disease, couples who were planning a pregnancy, and couples seeking prenatal testing. Newborn screening and general population screening, however, were not recommended.

Ethical Considerations

Before carrier screening can be offered to a high-risk population, the population must be educated about the disorder being screened, the basic tenets of carrier screening, and the potential benefits and risks of carrier screening. Screening for inherited disorders raises many complex issues. For example, screening raises a number of psychosocial issues, such as how an individual's self-esteem might be affected if he or she was found to carry a non-working gene). There are also implications for nonscreened family members if an individual is identified as a carrier. For instance, how will other family members be notified that they are also at risk for being a carrier. In addition, there is the potential for discrimination; other people may inaccurately infer that an individual who is a carrier has the inherited disorder.

Finally, and most importantly, no discussion of any type of genetic testing is complete without raising the topic of eugenics and the atrocities of the past that were associated with the abuse of genetic information. Today, each individual has the right to choose whether or not they want to know if they carry genes that predispose them to an inherited disorder. No one should be forced to learn about their carrier status, even by another family member. Moreover, the goal of any type of an inherited disorders screening program is not to eliminate genes that cause disease. Eliminating disease-causing genes would mean eliminating the human race. It is estimated that every human carries at least three to four genes that are associated with inherited diseases. Furthermore, there is a presumed constant rate of change (mutation) in human genetic material. These changes ensure variation amongst individuals. However, variation in human DNA occurs randomly, with some changes leading to beneficial effects, and some to detrimental effects like an inherited disorder. Therefore, genetic disorders will continue to occur and be a part of human genetic makeup. Although general population screening and population-targeted carrier screening raise many complex issues, they will ultimately allow society to better prepare for working with these disorders.

see also Cystic Fibrosis; Eugenics; Genetic Counseling; Genetic Counselor; Genetic Discrimination; Genetic Testing; Genetic Testing: Ethical Issues; Hemoglobinopathies; Metabolic Diseases; Tay-Sachs Disease.

Chantelle Wolpert

Bibliography

Levy H. L., and S. Alber. "Genetic Screening of Newborns." Annual Review of Genomics and Human Genetics 1 (2000): 139-177.

Internet Resources

American College of Medical Genetics. "Principles of Screening: Report of the Subcommittee of the American College of Medical Genetics Clinical Practice Committee." 1997. Policy Statement. <http://www.faseb.org/genetics/acmg/>.

Hall B., and S. Durham. "NIH Consensus Panel Makes Recommendations for Offering Genetic Testing for Cystic Fibrosis." NIH news release: April 16, 1997. <http://odp.od.nih.gov/consensus/cons/106/106_intro.htm>.