Associations Between the Four Toll-Like Receptor Polymorphisms and the Risk of Gastric Cancer: A Meta-Analysis

Purpose: The association between Toll-like receptor 2 (TLR2) -196 to -174del polymorphism and Toll-like receptor 4 (TLR4) polymorphisms (Asp299Gly, Thr399Ile, and 3725G>C) and gastric cancer risk are still conflicting. For better understanding of the effects of these four polymorphisms on gastric cancer risk, a meta-analysis was performed. Methods: An extensive search was performed to identify all case-control studies investigating such associations. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Results: A total of 21 studies (3,436 cases and 4,239 controls) were found to be eligible for meta-analysis. In the overall analysis, a significantly increased risk was observed in TLR4 Asp299Gly polymorphism (G allele vs. A allele: OR=1.84, 95%CI: 1.41, 2.39; GA vs. AA: OR=1.89, 95%CI: 1.43, 2.48; Recessive model: OR=1.90, 95%CI: 1.44, 2.49) and TLR4 Thr399Ile polymorphism (T allele vs. C allele: OR=1.97, 95%CI: 1.22, 3.18; TC vs. CC: OR=1.94, 95%CI: 1.19, 3.15; Recessive model: OR=1.98, 95%CI: 1.21, 3.21), whereas no associations were found in any genetic models of TLR2 -196 to -174del and TLR4 3725G>C polymorphisms. Similar results were found in the subgroup analyses by ethnicity. However, we detected that A allele carriers of the TLR4 Asp299Gly polymorphism might have an increase risk of gastric cancer in the Helicobacter pylori-positive population (G allele vs. A allele: OR=2.01, 95%CI: 1.22, 3.31). Conclusion: The results of this meta-analysis indicate that the TLR4 Asp299Gly and Thr399Ile polymorphisms are risk factors for gastric cancer development.