Polymorphisms Of Tlr4 And Gastric Cancer Susceptibility

Gastric cancer is a common cancer all over the world and it still remains a significant cancer burden. Gastric cancer is one of the key issues in cancer prevention and control strategy in China.Inflammation induced by H.pylori colonization in stomach is related to the development of gastric cancer and the genetic variations of genes of immune responses modify the host response to the infection. H.pylori lipopolysaccharide (LPS) is considered as one of the virulence factors involved in the gastritis, which induces secretion of proinflammatory cytokines, inducible NO and oxygen radicals by activating monocytes and gastric epithelial cells. TLR4 is involved in recognition of H. pylori and plays an important role in the gastroduodenal diseases and gastric carcinogenesis. Thus, we hypothesized that the genetic variation of TLR4 may be associated with the occurrence and development of gastric cancer.[Objective] The aim of this study was to evaluate whether polymorphisms in TLR4 gene(rs1927914 T>C and rs10759932 T>C), the key regulators of both innate and adaptive immunity, were related to susceptibility of gastric cancer in Chinese population.[Method] Two promoter variations of TLR4 (rs1927914 T>C and rs10759932 T>C) was genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1053 incident gastric cancer cases and 1100 cancer-free controls in a high-risk Han Chinese population.[Results] Compared with the wild-type homozygote (TT), individuals carrying C allele of rs10759932 had a significant reduced risk of gastric cancer (adjusted OR=0.81; 95%CI=0.67-0.96), and the protective effect was more obvious among the youngers, drinkers, non-smokers, and H.pylori infection status (P for heterogeneity > 0.05). No significant association with gastric cancer risk was observed for rs1927914 in this study population.[Conclusion] Our findings suggested that rs10759932 SNP may play a protective role in gastric carcinogenesis in Chinese population. Larger studies with different ethnic populations are warranted to confirm these findings.