Association between TNF-α-308 G/A gene polymorphism and gastric cancer risk: A systematic review and meta-analysis

Objective: Tumor necrosis factor-alpha (TNF-alpha) has been found to be associated with gastric carcinogenesis, but individually published results have been inconclusive. The aim of this study was to explore the relationship between the TNF-alpha-308 G/A polymorphism and gastric cancer risk. Methods: MEDLINE, EMBASE and the COCHRANE library databases were searched for relevant articles to identify all available data. The odds ratios (ORs) with 95% confidence intervals (95% CIs) from each study were used to assess the association between the TNF-alpha-308 G/A polymorphism and gastric cancer risk. Results: This meta-analysis included 30 studies (32 datasets) involving 7009 gastric cancer cases and 12,119 control subjects. Overall, a significant association was found between the TNF-alpha-308 G/A polymorphism and gastric cancer in AA + GA vs. GG (dominant contrast model) (OR = 1.20, 95% CI = 1.07-134, p = 0.001). With stratification based on ethnicity, the TNF-alpha-308 G/A polymorphism was correlated with gastric cancer risk in Caucasians, using the dominant contrast model (OR = 0.74, 95% CI = 0.57-0.96, p = 0.02), but not in East Asians and other ethnic groups. In the comprehensive subgroup analysis, a significant association was also found in recent articles (published after 2005), population-based high-quality studies, hospital-based high-quality studies, studies using the TaqMan method and non-cardia subgroups. However, the TNF-alpha-308 G/A polymorphism was not associated with specific histological types of gastric cancer risk. Conclusions: The TNF-alpha-308 G/A polymorphism may contribute to susceptibility to gastric cancer in Caucasians, especially for non-cardia gastric cancer, as most strongly demonstrated in high-quality studies and in studies using the TaqMan genotyping method. Furthermore, we recommend the TaqMan method as the preferred genotyping method in DNA polymorphism studies. (C) 2014 Elsevier Ltd. All rights reserved.