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APC E1317Q Is Not Associated with Colorectal Cancer in a Population-Based Case-Control Study in Northern Israel

¹ Department of Internal Medicine, Division of Molecular Medicine and Genetics; ² Department of Human Genetics, University of Michigan Medical School; ³ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan; ⁴ Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine; and ⁵ CHS National Cancer Control Center, Haifa, Israel

Requests for reprints: Stephen B. Gruber, Division of Molecular Medicine and Genetics, University of Michigan, 1524 BSRB, 109 Zina Pitcher, Box 2200, Ann Arbor, MI 48109-2200. Phone: 734-615-9712; Fax: 734-763-7672. E-mail: sgruber{at}umich.edu

A variant in the adenomatous polyposis coli gene, APC E1317Q, has been inconsistently associated with risk of colorectal cancer. We used data collected as a part of the Molecular Epidemiology of Colorectal Cancer study, a population-based study of colorectal cancer in northern Israel (1,834 matched cases and controls), to evaluate the relationship between this variant and risk of sporadic colorectal cancer. There was no association between E1317Q and colorectal cancer [odds ratio (OR), 1.15; 95% CI, 0.65-2.02]. When the control sample was restricted to polyp-free controls, the OR was 0.87 (95% CI, 0.36-2.14), indicating that this result is unlikely to be due to nondifferential misclassification due to undiagnosed polyps. A meta-analysis including these data and prior published reports found a nonsignificant summary OR nearly identical to the association reported here in the Molecular Epidemiology of Colorectal Cancer case-control study. Although there are previously published reports addressing this question, due to the low frequency of the variant, many of these studies lack the power to estimate the risk in a meaningful way. Given the substantial size of our study and the consistency of our findings with the results of our meta-analyses, we conclude that it is unlikely that APC E1317Q is associated with a clinically meaningful risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2325–7)