Background and Objective: Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori (H. pylori)-induced inflammation and may influence susceptibility to developing noncardia gastric cancer. Therefore, we investigated the effect of polymorphisms of TLR2, TLR4, and CD14, their combination and interaction with environmental factors on the noncardia gastric cancer risk in a Korean population.

Methods: We genotyped four polymorphisms in three genes (TLR2, rs1898830 A>G; TLR4, rs10759932 T>C, rs10983755 A>G; CD14, rs2569190 T>C) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which was stratified by the histological type of gastric cancer.

Results: TLR4 rs10983755 variant allele carriers were found to have a higher risk of intestinal type gastric cancer than homozygous wild-type carriers (OR [95% CI] = 1.40 [1.01–1.96], P = 0.046). Other genetic variants did not show any association with noncardia gastric cancer risk. When we examined the combined effect with other polymorphisms, the increased risk of intestinal type gastric cancer among TLR4 rs10983755 variant allele carriers compared to wild-type homozygous carriers were observed only among homozygous wild-type carriers of TLR2 rs1898830 (OR [95% CI] = 1.97 [1.24–3.12], P = 0.004) or CD14 rs2569190 (OR [95% CI] = 1.95 [1.31–2.91], P = 0.001). In addition, the effect of TLR4 rs10983755 variant allele on intestinal type gastric cancer was stronger among H. pylori-positive participants who are under 55 years old, smoke tobacco and drink alcoholic beverages.

Conclusion: These results suggest that the genetic polymorphisms of these innate immunity genes are associated with the development of H. pylori-associated noncardia gastric cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A64.