Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies

Background: Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies. Methods: This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed. Results: Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90–1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38–4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74–2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07–1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12–11.76, I2 = 97%). Under the heterozygous model, there was no ...