How People Respond to Gene Testing for Adult Onset Disorders

BALTIMORE--Patients choose genetic testing to help them make important life decisions, but often the risks and benefits are more complicated and less clear-cut than those of traditional medical tests, psychologist Ann-Marie Codori, PhD, of Johns Hopkins University, said at a seminar on genetic testing and counseling for adult onset disorders.

How individuals respond to the option or the outcome of genetic tests varies widely, depending on whether the disease is treatable, the test is for diagnosis or susceptibility, and individual coping styles. As examples, Dr. Codori compared testing for Huntington’s disease with that for hereditary nonpolyposis colorectal cancer (HNPCC).

Huntington’s is a progressive neuro-psychiatric illness caused by a single genetic defect. It is a rare phenotype, with few analogs. Everyone who inherits the mutation gets the disease, and the average age of onset is 40.

HNPCC, on the other hand, is only one of a number of possible causes of colon cancer, some genetic, some environmental. The test is really for susceptibility; about 80% of those testing positive will actually get the disease. Further, a negative result (when a mutation has not been previously identified in the family) does not rule out the disease, since tests are available for only two of five possible DNA mismatch repair genes linked with the syndrome, and scientists believe there are probably more mutations out there.

Patients testing positive for the Huntington’s gene, she said, are more likely to react adversely if they were expecting negative results. Many patients are upset after hearing information they can’t unlearn. She cited the case of a young man who wanted a family and took the test to "rule out" Huntington’s. He tested positive and expressed anger at his doctors and his wife, whom he later divorced.

A ‘Bad’ Reaction to ‘Good’ News

Adverse emotional reactions can also follow the "good" news of a negative Huntington’s test. This is more common among those who were expecting a positive test or who had already made an irreversible decision (like terminating a pregnancy) because they assumed Huntington’s was inevitable. Others, relieved of their own genetic burden, transfer their worries to untested family members.

Dr. Codori also found a generally worse psychological reaction among subjects who tested positive for Huntington’s when they were closer to the estimated age of disease onset, and were married and had no children. However, she said, group data can obscure the effect of testing on individuals. Some married patients, for instance, may have reacted badly because they were worried about their spouses.

Testing for HNPCC is different because real medical benefits can result: more vigilant cancer screening for those who test positive or elimination of screening for those who test negative. Because of this, patients who undergo testing may have an increased perception that they are in control of their health. Their worry may be reduced just by knowing their status and alerting other family members that they may be at risk.

Dr. Codori noted that a predictive test may not lead to changes in behavior. She followed 24 at-risk individuals who had inconclusive test results for HNPCC (that is, no mutation was found in the individual, but it wasn’t known for sure whether there was a mutation in the family). These people were urged to get a colonoscopy. Those who adhered to this advice tended to be older, had more affected relatives, and had less testing-related psychological stress than the nonadherent group.

A positive diagnostic test, she noted, can sometimes lead to a fatalistic decrease in preventive behaviors, like failing to return for follow-up mammograms. Finally, she said, genetic testing, can lead to discrimination by insurers. Worse yet may be the consequences of prenatal testing, as in the case of an HMO that wanted a member to end a pregnancy after the fetus was found to have cystic fibrosis.