Negative genetic test result in familial adenomatous polyposis: clinical screening implications

The goal of genetic testing is to define individual risk, which in turn may guide clinical management.

Thirty-two international familial adenomatous polyposis registries were surveyed regarding their approach to a specific clinical management question. There were 30 respondents. Respondents declared their clinical policy for an at-risk, first-degree relative who undergoes direct mutation analysis and does not have an APC gene mutation known to be present in his or her family.

Nineteen of 30 (63.3 percent) registries would discharge this negative APC mutation case from clinical screening. Eleven of 30 (37 percent) registries would maintain clinical screening. Reasons offered for maintaining surveillance included the need for additional confirmation of the APC mutation in two affected relatives, the possibility of sampling error or two different mutations in an affected family, limited prospective data, and patient anxiety.

The discrepancy in response to the survey suggests that some clinicians are as yet reluctant to accept fully that predictive genetic analysis is a definitive guide to clinical management in familial adenomatous polyposis. Nevertheless, we believe that use of a predictive gene test for familial adenomatous polyposis should alter management, decrease cost, and reduce psychological trauma for the tested individual. Although the benefit of APC analysis is accepted for the positive gene carrier, the challenge remains to reclassify the negative gene carriers who are no longer at risk for familial adenomatous polyposis.