Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis

BACKGROUND: Recent meta-analyses have studied population differences concerning interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to the IL-1 gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role of TNF-α-238 and TNF-α-308 gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta-analyzing all relevant studies to look for any differences concerning TNF-α gene polymorphisms in gastric carcinogenesis. METHODS: Extensive English language medical literature searches for human studies were performed up to the end of May 2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using the random-effects model. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: In seventeen studies, from various countries, the TNF-α-308 and TNF-α-238 frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients and controls. For TNF-α-308 frequency overall, the pooled ORs with 95%CI for genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145 (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses showed significant results for genotype G/G only in Asians [OR=0.774 (0.610-0.983), P=0.036]. CONCLUSION: In this meta-analysis there was an overall statistically significant increased cancer risk associated with TNF-α-308 G/G and A/A genotypes. Subgroup analyses showed significant results for genotype G/G in Asians, whereas no such significant results were found for Caucasians and Hispanics.