Cytokine Promoter Polymorphisms and Risk of Colorectal Cancer

Background: Cytokines and chemokines are involved in cancer development and progression, but their role in colorectal tumorigenesis is still far from well defined. This study investigated the association between five cytokine promoter polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC) in a hospital-based case-control study. Methods: A total of 377 Romanian subjects were included in this study: 144 patients with sporadic colorectal cancer and 233 controls. Cytokine polymorphisms (IL-1B -31T> C, IL-4R -3223C > T, IL-8 -251T > A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic discrimination TaqMan PCR assay with specific probes. Results: A significant association was observed for IL-10 -1082A> G polymorphism, the subjects carrying AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 -0.98) when compared with the more frequent AA genotype. Furthermore, in a dominant model the carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97). In a stratified analysis the only association between CRC and cytokine polymorphisms was found for carriers of IL-10 - 1082G allele and was restricted to poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was observed for the remaining polymorphisms and CRC risk. Conclusions: This study shows that IL-10 - 1082A> G polymorphism may influence CRC risk, the carriers of G allele being protected against CRC in the Romanian population.