Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of 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.
The analysis includes 3041 (1402 cases and 1639 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 1248 subjects (625 cases, 623 controls), and the second validation set consisted of 1793 subjects (777 cases, 1016 controls).
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; OR=0.76(0.52–0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity; OR=1.38(0.98–1.94).
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 GH/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted.