Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful.

Objective: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.

Activating mutation in MET oncogene in familial colorectal cancer.

Background: In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition.

Large intron 14 rearrangement in APC results in splice defect and attenuated FAP.

Familial adenomatous polyposis [FAP (OMIM 175100)] is an autosomal dominant colorectal cancer predisposition syndrome characterized by hundreds to thousands of colonic polyps and, if untreated by a combination of screening and/or surgical intervention, an approximately 99% lifetime risk of colorectal cancer. A subset of FAP patients develop an attenuated form of the condition characterized by lower numbers of colonic polyps (highly variable, but generally less than 100) and a lower lifetime risk of colorectal cancer, on the order of 70%. We report the diagnosis of three attenuated FAP families due to a 1.