Defining the overlap between sporadic and attenuated familial adenoma risk

Background Mutations in the APC gene lead to Familial adenomatous polyposis (FAP) and an attenuated form of this condition (AFAP). Based on previous work with mutation-verified patients from a large AFAP kindred, we showed that AFAP patients may be under-diagnosed, in the absence of a genetic diagnosis. For example, for patients between 30 and 79 years of age, 28% had fewer than 10 adenomas; 22% had fewer than 6 adenomas, and 7% had no polyps. Therefore, depending on the number of adenomas considered more consistent with sporadic, rather than a familial predisposition, and the availability or lack of known family history, up to ~25% of mutation-carrying AFAP patients may be missed in clinical practice. We sought to address this challenge by profiling mutation-independent adenoma formation among the mutation-negative carriers in this kindred.