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

Abstract

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. 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. 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. 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.