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Correlation of Asp299Gly and Thr399Ile polymorphisms in toll-like receptor 4 gene with digestive cancer risk: A meta-analysis.

The aim of this meta-analysis was to evaluate the correlation between the Asp299Gly and Thr399Ile polymorphisms in the toll-like receptor 4 (TLR4) gene and the risk of digestive cancer. A comprehensive search in PubMed, Web of Science (ISI), the China National Knowledge Infrastructure (CNKI), the Database of Chinese Scientific and Technical Periodicals (VIP) and the China Biology Medical (CBM) literature databases, including all the studies until May 25 2012, was conducted in order to investigate the abovementioned correlation. Statistical analysis was performed using STATA version 10.1. A total of 12 case-control studies were identified comprising 1,877 cancer patients and 3,181 controls for Asp299Gly polymorphism, and 8 case-control studies with 1,062 cancer patients and 1,867 controls for Thr399Ile polymorphism. Following sensitivity analysis and excluding studies that deviated from the Hardy-Weinberg equilibrium (HWE) in the controls, this meta-analysis demonstrated a significant correlation between the G allele of the Asp299Gly polymorphism and increased risk of gastric cancer in dominant [fixed-effect model (FEM): odds ratio (OR), 1.772; 95% confidence interval (CI), 1.340-2.343] and codominant (FEM: OR, 1.761, CI, 1.347-2.301) models. However, no significant correlation was detected for overall digestive and colorectal cancer. Furthermore, following the sensitivity analysis and exclusion of studies deviating from HWE in controls, no significant effect of the T allele of Thr399Ile polymorphism on overall digestive, gastric and colorectal cancer risk was demonstrated. This study suggests that the G allele of the TLR4 Asp299Gly polymorphism might be correlated with an increased risk of gastric cancer. However, this result needs to be further investigated by future studies.