Association between TNF-ɑ-308G/A polymorphism and esophageal cancer risk: An updated meta-analysis and trial sequential analysis

Background: TNF-α-308G/A (rs1800629) polymorphism has been previously implicated in the susceptibility to esophageal cancer, but results of these studies remained controversial or ambiguous. A meta-analysis was conducted to provide a more reliable conclusion about the association between TNF-ɑ-308G/A polymorphism and risk of esophageal cancer. Methods: Databases such as PubMed, EMBASE, Web of Science and CNKI were searched for relevant articles published till June 1, 2018. We used the pooled odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Subgroup analysis was carried out according to ethnicity, source of controls and genotyping method. A trial sequential analysis (TSA) was performed to reduce the risk of type I error and evaluate whether the results of our meta-analysis were credible. Results: A total of 9 published case-control studies with 1,435 esophageal cancer patients and 3,762 healthy controls were identified. Overall, our results indicated no significant correlation between TNF-α-308G/A polymorphism and increased risk of esophageal cancer in the fixed-effects model (allele model: pooled OR=1.11, 95% CI: 0.96-1.27, homozygote model: pooled OR=1.23, 95% CI: 0.77-1.95, heterozygote model: pooled OR=1.14, 95% CI: 0.97-1.35, dominant model: pooled OR=1.14, 95% CI: 0.97-1.34 and recessive model: pooled OR=1.00, 95% CI: 0.64-1.56). Subgroup analysis by ethnicity, source of controls and genotyping method showed no significant increase in the risk of esophageal cancer. TSA results need further investigation with a large sample size to certify such association. Conclusions: This meta-analysis study suggested no significant association between TNF-ɑ-308G/A polymorphism and the risk of esophageal cancer.