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The I1307K Adenomatous Polyposis Coli Gene Variant Does Not Contribute in the Assessment of the Risk for Colorectal Cancer in Ashkenazi Jews¹

Gastrointestinal Oncology Unit [H. S., E. B., M. G., D. K., L. S., Y. K., Y. D., L. A-B., H. S-D., N. A.], Department of Gastroenterology [H. S., R. K., Y. K., Y. D., L. A-B., Z. H., N. A.], and Department of Surgery B [A. K.], Tel-Aviv Sourasky Medical Center, Tel-Aviv 64-239; Sackler Faculty of Medicine [H. S., M. L., R. K., Z. H., N. A.] and Faculty of Management [M. L.], Tel-Aviv University, Tel-Aviv; and Technion Institute, Haifa [E. E., Y. E.], Israel

Ashkenazi Jews with the I1307K adenomatous polyposis coli gene variant were suggested to confer a higher risk for colorectal cancer (CRC). We assessed the clinical importance of this polymorphism in Israeli Jews at average and elevated risk for CRC. Among 1370 consecutive subjects that were examined, 975 Ashkenazi Jews were stratified into those at average risk (no personal or family history of colorectal neoplasia) and those at high risk. DNA was obtained from peripheral leukocytes and amplified by PCR, with primers designed to detect the I1307K variant. Overall, I1307K polymorphism was found in 7.1% (9.1% among Ashkenazi and 1.7% among non-Ashkenazi Jews). The carrier rate was 8.3 and 9.3% in average and high-risk Ashkenazim, respectively (P = 0.65). The overall odds ratio for neoplasia in carriers was 1.43 (95% confidence interval, 0.89–2.30). Age, gender, and the histopathological features of adenomas and cancers did not differ between carriers and noncarriers. No interaction on the CRC risk was found between I1307K variant and lifestyle modifiers (such as cigarette smoking, alcohol consumption, high body mass index, low physical activity, and vitamins/antioxidant intake). The I1307K adenomatous polyposis coli gene variant is not an important marker for increased risk for CRC. It confirms previous reports of a slight nonsignificant increase (OR, 1.4) in the risk of CRC in these carriers. There is no interaction effect on the risk of colorectal neoplasia between the I1307K variant and various lifestyle risk factors. The usual recommended screening and surveillance strategies should be used for carriers of this polymorphism.

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