Genetic Testing: Ethical Issues

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Genetic Testing: Ethical Issues

Genetic testing is the name given to a variety of laboratory techniques, all of which ultimately provide information about a person's underlying genetic makeup, also called their genotype. Genetic information is of interest because it can help in the diagnosis of a current health condition or provide insight into future health.

Advances in Genetic Science

Early understanding of genetic disease was first obtained about "single-gene disorders." These disorders include such diseases as sickle cell disease andcystic fibrosis. They occur because of the strong influence of a mutation in a single gene. Using the tremendous amounts of information about the human genome made available by the Human Genome Project, scientists are now dissecting the genetic components of complex disorders, such as diabetes and heart disease, that come about as a result of both genetic and environmental factors. Information about the genetic factors in complex disorders can help to predict the probability of future development of disease.

Understanding the issue of probability is important for the ethical use of genetic testing technology. "Genetic determinism" describes the idea that genes hold the map of an individual's future health. Although the detection of some mutations can diagnose the presence of a disease, many other tests provide only information about risk for disease, not a certainty that disease will develop. For example, genetic testing to detect mutations in the gene for breast cancer (BRCA1) can give information about an individual's susceptibility to developing breast and ovarian cancer. However, the probability of developing cancer will depend not only on the status of the gene, but also on factors related to family history and environmental exposures.

A Range of Ethical Issues

Ethical issues that arise within the context of genetic testing are similar to those that arise for any personal medical information. For example, there are concerns about protecting the privacy of the patient and the confidentiality of information, whether it is genetic data or any other item in the medical record. Possibilities of stigmatization or discrimination occur because of social perceptions of some diseases, whether the primary cause is genetic, infectious, or environmental. Furthermore, genetic testing requires informed consent; that is, patients need to be educated about the purpose of the testing (diagnosis, prognosis, or susceptibility assessment), the potential test outcomes and what they mean, and what the options are once the results are known.

Nevertheless, the perspective of "genetic exceptionalism" places genetic information in a category of different, special, or greater concern than other medical information. Knowledge of the genetic information of one person can have an influence on his family members because it implies information about their health status, disease risk, or the possibility of passing a condition on to their offspring. However, while concerns arise from genetic testing because of the obvious familial nature of genetic information, similar concerns arise from the simple knowledge of shared family history or environmental exposures, even without detailed genetic information.

Evaluation of the risks and benefits of genetic testing is an important factor in the process of considering the ethics of its use. The physical risks of genetic testing are generally minimal since, in most cases, DNA can be tested from easy-to-access cells: blood, buccal cells (inside of the cheek), and even hair follicles. However, there is a range of nonphysical risks, including loss of privacy and discrimination.

Consideration of the benefits of a genetic test is sometimes difficult. For example, when a therapy is available for a genetic disease, the availability of this benefit favors conducting the genetic test. If a therapeutic benefit is not available, however, the value of having this information becomes more questionable. Doctors and patients must ask if the information will help in some way, such as in life or reproductive planning. Although it can be difficult to compare the value of the information to the possible risks associated with conducting the genetic test, it should be carefully and explicitly considered.

Prenatal and Childhood Testing

Testing in children raises a different set of risks and issues. Adults are able to choose for themselves about genetic testing after hearing the relative advantages and risks. Children, however, must rely on their parents to decide for them. On the one hand, deciding to test children to diagnose a disease seems appropriate in most situations, particularly when a treatment can be provided. On the other hand, there is disagreement about testing children for disorders with adult onset and for which there is no intervention. In this situation, respect for the child's own decision (autonomy) and preserving privacy are ethical arguments for waiting to offer the genetic test. Upon reaching adulthood, individuals may then choose whether to learn their own genetic information.

Genetic testing requires additional considerations when done in the prenatal setting. In this case, parents are deciding to obtain genetic information about a third party, the developing fetus. In cases where there is no available medical therapy for a diagnosed genetic condition, the availability of limited options results in tough ethical choices for parents. The options may range from continuing the pregnancy, preparing for a child with special medical needs, or terminating the pregnancy. To make these decisions, prospective parents need clear information regarding the meaning of test results. Issues to consider include the predictive value of the test, the likely severity and age of onset of the predicted disorder, and the probability that the genetic alteration detected will actually result in a disorder.

Presymptomatic Testing: Huntington's Disease

Presymptomatic genetic testing when no treatment is available stands in contrast to genetic testing done for the diagnosis of a current disorder. Huntington's disease (HD) is an example of a genetic disorder in which clinical manifestations begin in adulthood. Although some symptoms can be managed with medications, no treatment is yet available to alter the gradual loss of muscle control, psychiatric changes, and progressive dementia .

HD is an autosomal dominant disorder, which means that an individual with only one abnormal copy of the HD gene will develop the disease, and the children of affected individuals have a 50 percent chance of inheriting the genetic mutation. The gene abnormality occurs when a polymorphic CAG repeat sequence is expanded beyond the normal number of 10 to 29 copies. Diagnosis of HD is almost 100 percent sure when the number of CAG repeats is in the range of 36 to 121.

Individuals at risk for HD may want to undergo genetic testing to end the uncertainty of not knowing whether they will be affected. This knowledge may allow for career and life planning. However, concerns that presymptomatic diagnosis of HD would lead to serious psychological distress or suicide led to the development of testing guidelines. The standard was established that all individuals who sought HD testing should receive pretest counseling to explain the test, assess their psychological status, and prepare them to consider their possible reactions to the results, whether positive or negative. In addition, results should be given in person, and counseling and support should be available following the test.

Before the identification of a specific gene for HD, genetic testing was done by linkage studies within a family. Linkage analysis required the voluntary participation of affected and unaffected family members across several generations. Identification of the specific gene defect now allows direct genetic analysis, without examining the DNA of any other family member. However, because of the inheritance patterns of HD, information about one family member can give diagnostic information about another. Figure 1 diagrams the ethical complexities arising from situations in which one family member's genetic test results in necessary implications for other family members. Note that it is not clear whether the individual desiring testing has decisive rights, or if those rights belong to those family members who do not desire such testing.

Susceptibility Testing: Apolipoprotein E

Susceptibility testing is another area that raises possible ethical issues for patients and clinicians. Recall that susceptibility implies that the genetic test does not provide the final answer regarding disease, but rather that additional factors are involved. For example, cardiovascular disease is a major source of morbidity and mortality. Polymorphic variants in the apolipoprotein E gene (APOE) have been found to be associated with variations in blood levels of lipids, lipoproteins, and apolipoproteins, which may in turn influence risk for heart disease. Clinicians and patients may wish to learn which APOE variants they have, to help determine their susceptibility to cardiovascular disease and the likelihood that altering their lifestyle risk factors or using pharmaceutical therapy might help prevent cardiovascular disease.

When deciding to test for APOE gene variants, however, there are additional consequences that must be considered, particularly the fact that the gene may play multiple roles in health and disease (pleiotropy ). Studies have shown that one version of APOE, the e4 allele , is associated with an increased risk of Alzheimer's disease. When deciding to undertake genetic testing for the intended immediate medical benefit of understanding cardiovascular disease risk, the individual should therefore also consider the possibility of learning potentially unwanted additional information.

Support Mechanisms

Several support mechanisms exist for dealing with the complex decisions and ethical issues arising from the medical application of genetic testing. In the past, much genetic testing has been carried out by medical specialists with disease-specific expertise who have an understanding of the medical, psychosocial, and family implications of diagnoses of particular genetic diseases. Genetic support groups have also been established for education and mutual support among patients and families with genetic disorders. An organization called the Genetic Alliance provides a referral source to connect individuals with appropriate support groups and information about genetic disorders.

Typically, the best resource for an integrated approach to support for patients and families is a genetic counselor. Genetic counselors provide factual education about genetic disease inheritance, how to understand risk and medical probabilities, and the range of options for care. They also provide counseling to help patients and families to clarify and articulate their own values and motivations in order to make the most appropriate decisions. These may be decisions about whether to undergo a genetic test or how they may act on receiving the results of a test.

see also Breast Cancer; Genetic Counseling; Genetic Counselor; Genetic Discrimination; Genetic Testing; Human Genome Project; Inheritance Patterns; Pleiotropy; Prenatal Diagnosis.

Carol L. Freund

and Jeremy Sugarman

Bibliography

Burgess, M. M. "Beyond Consent: Ethical and Social Issues in Genetic Testing." National Review of Genetics 2 (2000): 147-151.

Ross, L. F., and M. R. Moon. "Ethical Issues in Genetic Testing of Children." Archives of Pediatrics and Adolescent Medicine 154 (2000): 873-879.

Scriver, C. R., et al., eds. The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York: McGraw-Hill, 2001.

Welch, H. G., and W. Burke. "Uncertainties in Genetic Testing for Chronic Disease." Journal of the American Medical Association 280 (1998): 1525-1527.

Wilfond, B. S. "Genetic Testing." In Ethics in Primary Care, J. Sugarman, ed. New York: McGraw-Hill, 2000.