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November 4, 1998

Prescription for Prophecy: Confronting the Ambiguity of Susceptibility Testing

Author Affiliations

University of California San Francisco School of Medicine

University of California San Francisco School of Medicine

JAMA. 1998;280(17):1535-1536. doi:10.1001/jama.280.17.1535-JMS1104-4-1

It is but sorrow to be wise when wisdom profits not.—Tiresias in Sophocles' Oedipus Rex

The right to know is like the right to live. It is fundamental and unconditional in its assumption that knowledge, like life, is a desirable thing.—George Bernard Shaw, The Doctor's Dilemma

The words of the prophet Tiresias have been quoted by more than one geneticist attempting to capture the dilemma that arises when prophecy precedes cure.1,2 Tiresias challenges the value of foresight, given an impending disaster that cannot be averted. Shaw, in contrast, shows how knowledge can be elevated to the status of an unconditional right. How, then, should we advise the patient who inquires about a test that identifies a predisposition to a disease for which there is no definitive treatment?

This patient encounter is hardly a hypothetical one. Genetic tests that detect risk for conditions with familial components, such as Alzheimer disease, certain cancers, and even heart disease, have been the subject of much public and scientific discussion, not to mention commercial interest.

A test of this kind brings the patient to a crossroads at which he or she must confront a host of perplexing questions. Few susceptibility tests now available target a disease for which preventive or curative measures exist. Complicating the picture is the fact that these tests provide a suspicion of disease rather than a clear-cut prediction. Moreover, the predictive value of these tests may be heavily influenced by the population under study. It may be some time before routine testing in the general population for genes such as ApoE for Alzheimer disease or BRCA1 for breast cancer can be justified.

How should we address our patients' concerns about their risk status? A medical anthropologist once observed, "The very cognitive mastery that clinicians possess exposes them to the futility of intervention."1 Physicians may be tempted simply to dissuade patients who want to undergo testing or, alternatively, to concede to patients' wishes with little discussion. Both temptations are very real in the world of the 10-minute visit and quick turnaround; but to give way to these impulses is a grave mistake. Even if we can refer such patients to an expert, it remains our responsibility to know what options are available. In this essay, I offer some thoughts on how we can exercise this responsibility.

What It Means to Know

A fundamental task for the patient and the physician when considering genetic susceptibility testing is to determine what significance the genetic information holds for all involved parties. In its newsletter, The Marker, the Huntington Disease Society of America invited at-risk individuals to share their thoughts and feelings on predictive testing. A recurrent theme in these accounts was the intensely personal and far-reaching nature of genetic information.3 Many individuals commented that genetic information exposed something basic and intrinsic about their identity. Some spoke of the discovery of an immutable flaw and the burden of a tarnished self-image.

Nonetheless, many people desire genetic information, even after they are made to understand its enormity. In families with Huntington disease, individuals are often painfully aware of their risk, having lived for years with mixed hope and dread. Genetic counselors have found that many people feel paralyzed by their risk status and, as a consequence, have difficulty moving in any purposeful direction. The patient's decision to undergo testing often reflects a desire to move forward in some way, and to end a long-standing struggle with anxiety and uncertainty.1

Foreknowledge about disease affords individuals time to strengthen support systems and reshape personal goals. This knowledge can guide plans regarding child-bearing and careers. It can teach people to let go of the trivial things that threaten to spoil a moment and empower them to take action prior to the onset of illness. These measures may include joining a support group and moving closer to family or, alternatively, finding a one-story home and making appropriate financial arrangements. A discussion about end-of-life options might be initiated, if it has not already begun.

Choosing Not to Know

Physicians need to recognize that not all patients want to know their risk status, and many may be ambivalent about pursuing susceptibility testing. In a survey of individuals at risk for Huntington disease, 15.5% of the sample reported that they would not want to take the predictive test; 19.4% were simply not sure.4 These percentages may be even greater for susceptibility testing. We should remind patients that they can decline testing. Our respect for one patient's decision to forego testing should match our respect for another's desire to pursue it.

Susceptibility testing may have considerable psychological repercussions. Studies among women who have received cancer risk information suggest that test results have a profound emotional impact.5 The trauma of learning that one has the gene for an untreatable disorder may be even greater. One study suggested that about 2% to 6% of persons at risk for Huntington disease may have severe psychiatric or suicidal responses to a positive test result.6 Even recipients of a negative result may be haunted by "survivor guilt" on learning that they have eluded a disease that has taken others in their family.2

Genetic test results do not always afford individuals the peace of mind they seek. The question of whether they will get the disease can be substituted for the question, when will they become symptomatic? Furthermore, the results may be inconclusive. A whether can easily become an unconditional when in the patient's mind, if the significance of test results is not thoroughly explained. Patients' anxieties can also be multiplied when few treatment options exist that are not costly, ineffective, or harmful. Physicians should remind patients that, regardless of whether they chose to undergo testing, they always have the opportunity to reassess and restructure their lives.

Issues in Communication

Before undergoing testing, the patient should be counseled about the likelihood and implications of a positive result and what they can expect about quality of life in the event of disease. A discussion of available resources and support services is also essential. Questions regarding the test itself have to be anticipated and answered: How costly is the test? What are its limitations?

The social repercussions of testing also warrant careful evaluation. For example, patients' insurance coverage may be jeopardized by genetic testing. Employment discrimination is another concern. It has been shown that employers are less likely to hire individuals with a personal or family history of medical problems.2 While there are few data on the extent of these risks to patients, these possibilities have held considerable influence in decision making.7 In light of these possibilities, confidentiality must also be addressed.

This process of educating patients has many subtleties. The sensitivity, specificity, and positive predictive value of a test; the penetrance of a given gene; and the efficacy of risk reduction behaviors are all complex concepts that are not necessarily understandable to the anxious patient. The language of risk itself poses challenges. The term predisposition is extraordinarily slippery. Predisposed does not mean predestined. Genetic counselors may try to avoid words such as "higher" or "unlikely" for fear of influencing the patient's choices. Numerical expressions of risk can, in turn, give a false impression of accuracy and certainty. It is therefore essential that physicians present information in a manner appropriate to the patient's level of understanding.

Final Thoughts

Too often, the patient's role in decision making is undermined by the hurried nature of medicine. I have heard the assertion "I've consented the patient" uttered as though informed consent were something to be foisted upon the patient. Ideally, informed consent and follow-up counseling should be an ongoing dialogue between patient and physician—wherein the patient participates as an active subject and not simply as a receptacle for information. The decision to undergo testing ultimately resides with the patient—we cannot lose sight of this simple fact.

Neither Tiresias' despairing pessimism nor Shaw's unconditional right-to-know provides an adequate framework for approaching the patient in question. The ideal physician is a skilled teacher who balances thoughtful guidance with careful attention to the patient's individual needs. It is inappropriate for us to impose our personal values on our patients, and it is equally unacceptable for us to dispense information indiscriminately, only to sit back in silence as patients agonize, alone, over a final decision. Our fundamental challenge, as physicians entering the era of molecular medicine, is to temper our newfound wisdom with an open-minded appreciation of the unique needs of each individual we serve.

Wexler  NS The Tiresias complex: Huntington's disease as a paradigm of testing for late-onset disorders.  FASEB J. 1992;62820- 2825
Andrews  LB Assessing Genetic Risks: Implications for Health and Social Policy.  Washington DC National Academy Press1994;146- 147268
Quaid  K A few words from a "wise" woman. Weir  RFLawrence  SCFales  Eeds Genes and Human Self-knowledge: Historical and Philosophical Reflections on Modern Genetics. Iowa City University of Iowa Press1994;5
Markel  DSYoung  ABPenney  JB At risk persons' attitudes toward presymptomatic and prenatal testing of Huntington disease in Michigan.  Am J Med Genet. 1987;26295- 305Article
Croyle  RTSmith  KRBotkin  JRBaty  BNash  J Psychological responses to BRCA1 mutation testing: preliminary findings.  Health Psychol. 1997;1663- 72Article
Kessler  SField  JWorth  LMosbarger  H Attitudes of persons at risk for Huntington's disease toward predictive testing.  Am J Med Genet. 1987;26259- 270Article
Biesecker  BBBrody  LC Genetic susceptibility testing for breast and ovarian cancer: a progress report.  J Am Med Womens Assoc. 1997;5122- 27