Genetic variants in the regulation region of TLR4 reduce the gastric cancer susceptibility.

Abstract

Gastric cancer (GC) is one of the most common cancers diagnosed in China. It has been suggested that the genetic polymorphisms of Toll-like receptors (TLRs) might be in close relation to tumorigenesis and development of gastric cancer. In this study, we performed a case-control study to investigate the genetic polymorphisms of TLR3, 4, 5, 7 with the genetic susceptibility of gastric cancer. TLRs gene polymorphisms in 471 gastric cancer (GC) patients and 471 healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis or TaqMan assays. Odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the association of TLR4 variants with the GC risk via unconditional logistic regression. Our results suggested that variant genotypes of TLR4 rs7869402 (OR=0.61, 95%CI=0.40-0.92, P=0.02) and TLR4 rs7873784 (OR=0.17, 95%CI=0.09-0.33, P<0.01) gene polymorphisms reduced the risk of GC. Stratified analysis showed that rs7869402 T-containing genotype significantly decreased the susceptibility of GC among females (OR=0.38, 95%CI=0.16-0.91, P=0.03), older subjects (OR=0.48, 95%CI=0.26-0.87, P=0.02), non-smokers (OR=0.41, 95%CI=0.23-0.71, P<0.01) and non-drinkers (OR=0.58, 95%CI=0.30-0.78, P<0.01). In case of rs7873784 polymorphism, C-containing genotype reduced the risk of GC among males (OR=0.08, 95%CI=0.03-0.21, P<0.01), but not among females (OR=0.53, 95%CI=0.22-1.27, P=0.15). As to the other four SNPs (TLR3 rs5743303, TLR4 rs1927914, TLR5 rs1640816 and TLR7 rs3853839), no significant correlations were found to be related to the risk of gastric carcinoma. Our research demonstrated the significance of TLRs polymorphisms in decreasing the risk of GC.