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Recreational Physical Activity Modifies the Association Between a Common GH1 Polymorphism and Colorectal Cancer Risk

¹ Department of Community Medicine and Epidemiology, Clalit Health Services National Cancer Control Center, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Departments of ² Internal Medicine, ³ Epidemiology, and ⁴ Human Genetics, University of Michigan Schools of Medicine and Public Health, Ann Arbor, Michigan

Requests for reprints: Gad Rennert, Clalit Health Services National Cancer Control Center, at Carmel Medical Center, Haifa 34362, Israel. Phone: 972-4-825-0474; Fax: 972-4-834-4358. E-mail: rennert{at}tx.technion.ac.il

Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical activity with colorectal cancer risk in a case-control study.

Methods: The analysis includes 3,041 (1,402 cases and 1,639 controls) participants in the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study in Northern Israel. Analysis was carried out separately in two sets. The first set included 1,248 subjects (625 cases, 623 controls), and the second validation set consisted of 1,793 subjects (777 cases, 1,016 controls).

Results: No association was found between the studied polymorphism and CRC risk. However, evaluation of gene environment interactions revealed an interaction between leisure time physical activity and the GH1 polymorphism, which was consistent in both sets (P_interaction = 0.005). The genotype AA was associated with decreased risk of CRC among individuals who did not engage in any such activity (odds ratio, 0.76; 95% confidence interval, 0.52-0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity (odds ratio, 1.38; 95% confidence interval, 0.98-1.94).

Conclusions: We found that the A allele of the rs2665802 polymorphism is associated with reduced risk of CRC only among physically inactive individuals, indicating an interaction between physical activity and the growth hormone/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3314–8)