Effects of Polymorphisms of Innate Immunity Genes and Environmental Factors on the Risk of Noncardia Gastric Cancer

PURPOSE: Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. MATERIALS AND METHODS: We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. RESULTS: TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. CONCLUSION: The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.