Effect of the -2081G/A polymorphism of the TLR4 gene and its interaction with Helicobacter pylori infection on the risk of gastric cancer in Chinese individuals

Genet Test Mol Biomarkers. 2014 Sep;18(9):610-5. doi: 10.1089/gtmb.2014.0047. Epub 2014 Aug 1.

Abstract

Aims: Toll-like receptor 4 (TLR4) plays an important role in gastric carcinoma. Using a case-control study, we analyzed the genotypic distribution of TLR4 rs10983755 (-2081G/A) and rs11536878 in a Chinese population and investigated the effect of their interactions with Helicobacter pylori infection on susceptibility to gastric cancer (GC) and atrophic gastritis (AG).

Methods: In this study, 409 and 581 cases of GC and AG, respectively, were selected for analyses along with an equal number of matched controls. The TLR4 polymorphisms were genotyped using Sequenom MassARRAY. Serum levels of anti-H. pylori IgG were determined by enzyme-linked immunosorbent assay.

Results: The TLR4-2081G/A polymorphism was negatively associated with GC (AG+AA vs. GG: odds ratio [OR]=0.70, 95% confidence interval [CI]=0.53-0.93, p=0.012). A decreased risk of GC was observed in H. pylori negative and TLR4-2081(AG+AA) genotype subjects [H. pylori(-)/AG+AA vs. H. pylori(+)/GG: OR=0.16, 95% CI=0.09-0.27, p<0.001]. The rs11536878 polymorphism was not associated with GC or AG.

Conclusions: The TLR4-2081G/A polymorphism seems to affect the risk of gastric carcinogenesis and may to some degree play a protective role against H. pylori infection.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bacterial / blood
  • Asian People
  • Case-Control Studies
  • China
  • Genotype
  • Helicobacter Infections / blood
  • Helicobacter Infections / genetics*
  • Helicobacter pylori*
  • Humans
  • Middle Aged
  • Polymorphism, Genetic*
  • Risk
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / genetics*
  • Toll-Like Receptor 4 / blood
  • Toll-Like Receptor 4 / genetics*

Substances

  • Antibodies, Bacterial
  • TLR4 protein, human
  • Toll-Like Receptor 4