Background/Aims: Familial adenomatous polyposis is caused by germline mutation of the adenomatous polyposis coli (APC) gene. Affected individuals develop hundreds of colorectal adenomas at young age and can have extracolonic lesions. Methods: This study evaluated the phenotype of 74 patients with familial adenomatous polyposis from 11 unrelated families with an identical 5-base pair deletion at codon 1309 of the APC gene. Results: Polyp density in the sigmoid colon of 16 patients from 9 families varied from 3.8 to 13.1/ cm2, and mean polyp diameter ranged from 1.4 ± 0.1 to 2.7 ± 0.1 mm. The distribution of colonic adenomas also varied, with diffuse polyposis in 6 patients but relative polyp sparing in the more proximal colon in 6 others. Age at diagnosis of colorectal cancer ranged from 19 to 62 years, but the mean age did not differ among the 4 families with multiple cases. Colorectal cancers occurred predominantly in the rectosigmoid (80%) but also in the more proximal colon. The percentage of patients affected by various extracolonic lesions differed widely among and within the 11 families (range, 0%-100%). Conclusions: APC gene mutation at codon 1309 results in intrafamily and interfamily phenotypic variation in familial adenomatous polyposis. Environmental and/or other genetic factors must play roles in the expression of germline APC gene mutations.
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