Tumor Necrosis Factor-α-308 G/A Polymorphisms and Risk of Hepatocellular Carcinoma: A Meta-Analysis

Context: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-alpha (TNF-alpha) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-alpha promoter (TNF-alpha-308) and HCC risk has been confirmed in various reports. Evidence Acquisition: The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF-alpha -308 and the risk of HCC. To determine this association, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4% vs. 8.4%). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95% CI = [1.26-2.50]; P value < 0.002). In addition to the allelic model, the dominant model (AA + AGvs. GG) was significantly associated with HCC risk (OR = 1.80; CI = [1.29-2.51]; P value < 0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG + GG), no trustworthy associations with the risk of HCC development were observed. Conclusions: This meta-analysis indicated that the TNF-alpha -308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-alpha -308 G/A polymorphisms associated with HCC.