Negative genetic test result in familial adenomatous polyposis - Clinical screening implications

PURPOSE: The goal of genetic testing is to define individual risk, which in turn may guide clinical management. METHODS: Thirty-two international fami lial adenomatous polyposis registries were surveyed regarding their approac h to a specific clinical management question. There were 30 respondents. Re spondents declared their clinical policy for an at-risk, first-degree relat ive who undergoes direct mutation analysis and does not have an APC gene mu tation known to be present in his or her family. RESULTS: Nineteen of 30 (6 3.3 percent) registries would discharge this negative APC mutation case fro m clinical screening. Eleven of 30 (37 percent) registries would maintain c linical screening. Reasons offered for maintaining surveillance included th e need for additional confirmation of the APC mutation in two affected rela tives, the possibility of sampling error or two different mutations in an a ffected family, limited prospective data, and patient anxiety. CONCLUSIONS: The discrepancy in response to the survey suggests that some clinicians ar e as yet reluctant to accept fully that predictive genetic analysis is a de finitive guide to clinical management in familiar adenomatous polyposis. Ne vertheless, we believe that use of a predictive gene test for familial aden omatous polyposis should after management, decrease cost, and reduce psycho logical trauma for the tested individual. Although the benefit of APC analy sis is accepted for the positive gene carrier, the challenge remains to rec lassify the negative gene carriers who are no longer at risk for familiar a denomatous polyposis.