Assay for Detecting the I1307K Susceptibility Allele within the Adenomatous Polyposis ColiGene.

Most germline mutations of the adenomatous polyposis coli (APC) tumor suppressor gene result in a classic inherited cancer syndrome called familial adenomatous polyposis (FAP). FAP is characterized by thousands of colonic polyps, well-defined extracolonic manifestations that may include pigmented lesions of the ocular fundus, supernumerary teeth, osteomas, odontomas, desmoid tumors and epidermoid cysts, and a 100% lifetime risk of developing colorectal cancer. Shortly after the APC gene was cloned in 1991 (1,2) the molecular basis of an attenuated form of FAP was recognized to be related to germline mutations within APC that were most likely to be found in the 5' and 3' ends of the gene (3,4). The truncating mutations leading to classic FAP and attenuated FAP are quite rare, but recently a polymorphism of the APC gene was found among 6 to 7% of Ashkenazi Jews that approximately doubles the risk of colorectal cancer (5).