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

Authors Theodoros Rokkas, Panos Sechopoulos, Dimitrios Pistiolas, Fotis Kothonas, Georgios Margantinis, Georgios Koukoulis.


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.

Keywords TNF-α-308 gene, TNF-α-238 gene, polymorphism, gastric cancer, meta-analysis

Ann Gastroenterol 2014; 27 (2): 139-148

Original Articles