A Nonsynonymous Polymorphism in IL23R Gene Is Associated With Risk of Gastric Cancer in a Chinese Population

Interleukin-23 receptor (IL-23R) is a key element in T helper (Th) 17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case-control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR)=0.78, 95% confidence interval (CI)=0.68-0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR=0.75, 95% CI=0.65-0.87) other than in diffuse-type gastric cancer (adjusted allelic OR=0.96, 95% CI=0.76-1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population. Mol. Carcinog. (C) 2010 Wiley-Liss, Inc.