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A Common 8q24 Variant and the Risk of Colon Cancer: A Population-Based Case-Control Study

Departments of ¹ Family Medicine-Research Division, ² Epidemiology and Biostatistics, and ³ Reproductive Biology, Case Western Reserve University/University Hospitals of Cleveland; ⁴ Case Center for Transdisciplinary Research on Energetics and Cancer, Case Comprehensive Cancer Center; ⁵ Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; and ⁶ Cancer Control Program, University of Kentucky, Lexington, Kentucky

Requests for reprints: Li Li, Department of Family Medicine-Research Division, Case Western Reserve University, 11001 Cedar Avenue, Suite 306, Cleveland, OH 44106-7136. Phone: 216-368-5437. E-mail: lxl62{at}cwru.edu

Three recent studies identified common variants on 8q24 that confer modestly increased susceptibility to colorectal cancer. Here, we replicate the association in a population-based case-control study of colon cancer, including 561 cases and 721 unrelated controls. The rs6983267 marker was significantly associated with colon cancer risk. Compared with those homozygous for the T allele, the heterozygous and homozygous carriers for the G allele had an age-adjusted odds ratio of 1.39 (95% confidence interval, 1.03-1.88) and 1.68 (95% confidence interval, 1.21-2.33), respectively. An additive model showed strong evidence for a gene-dose response relationship (P_trend = 0.0022). The association remained statistically significant when restricted to Caucasians only (527 cases and 679 controls; P_trend = 0.0056). Further adjustment for other known risk factors did not alter the results. Stratified analysis revealed no evidence for effect modification by family history of colorectal cancer, age, or gender. These data replicate the association identified from recent studies, providing additional evidence supporting the rs6983267 genetic polymorphism as a marker predisposing to colon cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(2):339–42)

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