Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis

Background Studies investigating the associations between tumor necrosis factor-alpha (TNFA) polymorphisms and hepatocellular carcinoma (HCC) risk report conflicting results. We conducted a meta-analysis to assess the association between TNFA gene TNFA-308(G/A), TNFA-238(G/A), TNFA-863(C/A), TNFA-857(C/T), TNFA- 1031 (T/C) polymorphisms and HCC susceptibility. Methods Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for TNFA polymorphisms and HCC were calculated in a fixed-effects model (the Mantel– Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results This meta-analysis included 17 case–control studies, which included 2,357 HCC cases and 3,161 controls. Overall, the variant genotypes AA/AG of -308G/A were associated with a significantly increased HCC risk, when compared with GG genotype (AA vs. GG, OR = 1.97, 95%CI = 1.01–3.83; AG vs. GG, OR = 1.88, 95%CI = 1.23–2.88; AA/AG vs. GG, OR = 1.80, 95% CI = 1.19–2.72). When stratifying for ethnicity, significantly elevated HCC risk was found among Asians. Moreover, similar results were observed between TNFA- 238G/A, TNFA-863C/A polymorphisms and HCC risk among Asians (for -238G/A, AG vs. GG OR = 1.63, 95%CI = 1.17–2.26, AA/AG vs. GG OR = 1.61, 95%CI = 1.16–2.24; for -863 C/A, AC vs. CC OR = 1.72, 95% CI = 1.03–2.88, AA/AC vs. CC OR = 1.71, 95%CI = 1.02–2.86), while no associations were observed between TNFA-857C/T, TNFA-1031T/C polymorphisms and HCC susceptibility. Conclusions This meta-analysis shows that TNFA-308G/ A, TNFA-238G/A and TNFA-863C/A polymorphisms may be associated with HCC among Asians. TNFA-857C/T and TNFA-1031T/C polymorphisms were not detected to be related to the risk for HCC.