Tumor Necrosis Factor-α 238 G/A Polymorphism and Risk of Hepatocellular Carcinoma: Evidence from a Meta-analysis

Background: Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progressionof cancer. Many epidemiological studies have evaluated associations between the TNF-α 238 G/A polymorphismand hepatocellular carcinoma (HCC) risk, but the published data are inconclusive. Therefore, we performed thepresent meta-analysis.
Methods: Electronic searches of several databases were conducted for all publicationson the association between TNF-α 238 G/A polymorphism and HCC through July 2012. Asummary odds ratio(OR) with its 95% confidence interval (CI) were calculated to evaluate the strength of this association.
Results:Eleven case-control studies with a total of 1,572 HCC cases and 1,875 controls were finally included in thismeta-analysis. Overall, the TNF-α 238 G/A polymorphism was significantly associated with increased risk ofhepatocellular carcinoma in three genetic comparison models (For A versus G: OR 1.32, 95%CI 1.04-1.69, P =0.02, I2 = 40%; for AG versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.03, I2 = 40%; for AA/AG versus GG: OR1.33, 95%CI 1.03-1.72, P = 0.03, I2 = 41%) when all studies were pooled. Subgroup analysis by ethnicity furthershowed that there was a significant association between the TNF-α 238 G/A polymorphism and risk of HCC inAsians under three genetic comparison models (For A versus G: OR 1.30, 95%CI 1.00-1.68, P = 0.05, I2 = 45%for AA/AG versus GG: OR 1.31, 95%CI 1.00-1.71, P = 0.05, I2 = 46%).
Conclusions: This meta-analysis providedconvincing evidence that the TNF-α 238 G/A polymorphism is associated with increased susceptibility to HCC.However, more well-designed studies with large sample size are needed to validate this association in Caucasians.