The results of our multicenter study indicate that cancer risk perception in individuals undergoing genetic evaluation for Lynch syndrome varies significantly with the genetic test result, and that a significant proportion of individuals who are at high risk for CRC underestimate their risk. In our study, 90% of individuals with a true-positive genetic test result correctly recognized their CRC risk as increased; however, 38% with indeterminate test results did not believe their risk of CRC was above average, and 36% of individuals with true-negative results misinterpreted their CRC risk. Individuals previously diagnosed with Lynch syndrome–associated cancer were more likely to underestimate their risk of developing a second CRC. Women with inaccurate CRC risk perception were also less likely to accurately assess their risk of endometrial cancer.
Studies of cancer risk perception in patients undergoing testing for familial cancer syndromes have predominantly included patients at risk for hereditary breast and ovarian cancer,11–13
and few studies include patients at risk for Lynch syndrome.14,15
Although to our knowledge, there have been no published studies evaluating CRC risk perception in individuals with indeterminate results for Lynch syndrome, a study of 500 women who underwent testing for BRCA1/2
genes demonstrated lower perceived cancer risk in women with indeterminate results compared with carriers.11
These results lend support to our findings that individuals with indeterminate results may be falsely reassured even though their risk of CRC is still above that of an average individual. Family cancer history has been demonstrated to influence risk perception,16
and in our study, nearly all the individuals with true-negative results who had overestimated their CRC risk had a family cancer history that met the Amsterdam criteria for Lynch syndrome. Indeed similar findings of a pessimistic bias have been noted in women with true-negative BRCA
results who have a family history of breast cancer.17
The underestimation of CRC risk in subjects with a history of Lynch syndrome–associated cancer is more complex. It is possible that these individuals believed that because they had been diagnosed with cancer in the past, their risk of developing a second CRC was lower. It is also possible that the optimistic bias in these motivated subjects may have resulted from the perception that recurrent CRC was preventable with endoscopic screening.
It is important to consider potential limitations of our study. First, our method of estimating cancer risk was complex because patients were asked for a comparative assessment of risk in relation to an average individual. This method of qualitatively estimating cancer risk has been widely used, and individuals were able to make clinically important distinctions about whether they thought their risk was the same as the average individual their age or their risk was higher or lower. In addition, the use of numerical values is inherently more cognitively challenging and may result in misclassification.18
Nevertheless, there is surely inherent individual variation in how participants interpreted the question that is difficult to control for.19
Second, paticipants were enrolled through specialized cancer centers and were highly motivated individuals. Our results likely represent an optimistic view of accurate risk perception of genetic test results in general. Third, we broadly defined appropriate CRC screening among patients who underwent genetic testing for Lynch syndrome. Additional studies are needed to systematically evaluate compliance with screening because recommendations vary based on patient history as well as on results of molecular evaluation. Fourth, although the general approach to genetic testing was similar across sites, genetic counseling was not standardized as part of the study. Therefore, variations in how and what information was presented by providers and its integration in the follow-up care of patients would inevitably have existed. Our goal was not to study the effect of a standardized genetic counseling intervention on risk perception, but to focus on the specific outcome of risk perception based on test results. Our findings indicate that hereditary CRC risk counseling may need to include syndrome-specific experts as well as guidance from behavioral scientists to ensure the most effective communication. As genetic testing becomes more prevalent, attention will need to be paid to the content of risk information as well as how it is delivered. Variability in extent and type of counseling as well as individual psychosocial variables may constitute critical factors for patients' understanding of their test results.
Our results also have important downstream implications. Studies have suggested that genetic test results may influence uptake of screening, prophylactic surgery, and the dissemination of risk information to relatives.20–24
Indeed in our study, individuals with inaccurate CRC risk perception were less likely to have appropriate CRC screening, and women were also more likely to inaccurately assess their risk of endometrial cancer. Thus, it is important to explore the reasons for inappropriate risk perception. Individuals' perception of their cancer risk may be affected by their understanding and retention of genetic test results, variation in communication of risk by their health care providers, and a host of other factors including their personal and family history of cancer. Interpretation of genetic test results can be complicated, and the concept of an indeterminate result is often confusing even for physicians ordering these tests. A study by Giardiello et al in individuals with familial adenomatous polyposis that evaluated the use of commercial APC
gene testing found that in 31.6% of cases, physicians may have misinterpreted test results because of an indeterminate finding.25
What can be done to improve cancer risk perception? Guidelines recommend pre- and post-test counseling and discussion of the implications of genetic predisposition testing.26
Although the genetic counseling process was not standardized as part of the study, all patients who undergo genetic testing at our institutions are seen by a certified or board-eligible genetic counselor, and the majority of patients also meet with either an oncologist or gastroenterologist with training in genetics at the same visit. Although patients are frequently referred by primary care providers, testing is initiated in the high-risk clinic after pretest counseling. Patients are requested to return for post-test counseling regardless of their result, and in only a few cases are results disclosed via telephone. In those rare circumstances, patients are invited to return for another in-person visit. In our study, 89% of individuals reported being seen by a genetic counselor or in a high-risk clinic. Despite these ideal circumstances under which testing and counseling were performed, 20% of individuals inappropriately estimated their cancer risk. With an increase in direct-to-consumer marketing of genetic testing, there is an even higher risk of the misinterpretation of genetic test results.
Our findings underscore the complexity in risk communication. Studies are needed to systematically evaluate both patient- and physician-related factors responsible for inappropriate perception of risk in order to develop effective interventions. Physician and patient education are necessary so that indeterminate genetic test results do not provide false reassurance. The use of standardized educational material that outlines the implications of test results and recommendations for management may minimize variability in information provided to patients, facilitate knowledge retention, and provide specific screening recommendations for individuals who remain at high risk.
In addition, particularly for indeterminate test results, there needs to be longitudinal follow-up and reinforcement of the meaning of the test results. These patients may benefit from additional genetic counseling and from reinforcement from the primary care physician who observes the patient on a long-term basis after the genetic counseling and testing encounter is completed. The benefits of reinforcement would not be limited to individuals with true-positive and indeterminate results, but would also be available to individuals with true-negative results.
Our study was limited to patients at risk for a highly penetrant inherited cancer syndrome, for which interpretation of true-positive and true-negative results is relatively straightforward in terms of cancer risk and screening recommendations. As additional moderate- and low-susceptibility genes are identified, the implications of even a positive result are likely to be complex and may depend on a variety of factors, including the relationship with other genes, environment, and behaviors. Understanding how patients interpret such information and developing strategies to enhance communication of benefits and limitations of genetic testing is an area worthy of continued study.