APC I1304K increases risk of transition from polyp to colorectal carcinomain Ashkenazi jews

Background & Aims: The I1307H allele of the APC gene has been shown to conf er a modestly elevated risk of colorectal cancel in the Ashkenazi Jewish po pulation (relative risk, 1.5-1.7). However, it is unclear whether the alter ation predisposes to adenomas and whether the genetic information can be us ed in clinical practice. To further address the pathogenic significance of I1307H, we offered both a genetic test and a screening program to individua ls considered to be at increased risk for colorectal cancer. We compared th e prevalence of polyps and their characteristics between carriers and nonca rriers. Methods: Invitations to participate in a DNA and colonoscopy screen ing program were mailed, together with a family questionnaire, to 3540 hous eholds forming the Jewish Community in Ottawa. The I1307K variant was analy zed in 242 eligible respondents who were selected because they had a person al or family history of colon cancer. Nearly 80% of these respondents (n = 189; age range, 32-83 years) consented to undergo a single colonoscopic exa mination. Results: The overall carrier frequency of I1307K in the study gro up was 10.3%. A higher proportion of heterozygous gene carriers was found i n the subgroup of colon cancer survivors (27%) than among asymptomatic indi viduals (8%, P < 0.02). A total of 59 polyps were identified in 44 subjects . Histologically confirmed adenomatous polyps were diagnosed in 11.8% of ca rriers and 12.8% of noncarriers (P > 0.5). No significant differences in po lyp size, multiplicity, location, degree of villosity, or age-dependent pre valence were found between the 2 groups of participants. Conclusions: The h igh frequency of I1307K colorectal cancer patients found in the Ashkenazi J ewish community of Ottawa and the equivalent proportion of carriers and non carriers who developed adenomatous polyps suggest that in this community, I 1307K is associated with a significant predisposition to carcinoma but not adenoma.