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Polymorphisms of the TLR4 gene and risk of gastric cancer
Authors:Lina Huang  Kexin Yuan  Jingjing Liu  Xiyun Ren  Xiaoqun Dong  Wenjing Tian  Yunhe Jia
Institution:1. Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China;2. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, USA;3. Department of Colorectal Cancer Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, PR China
Abstract:

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.
Keywords:GC  gastric cancer  TLR4  Toll-like receptor 4  OR  odds ratio  CI  confidence interval  LPS  lipo-polysaccharide  PCR-RFLP  polymerase chain reaction-restriction fragment length polymorphism  TLRs  Toll-like receptors  TNM  tumor-node-metastasis  HWE  Hardy&ndash  Weinberg equilibrium  EPA  eicosapntemacnioc acid  DHA  docosahexaenoic acid
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