Comprehensive assessment of the association between tumor necrosis factor alpha G238A polymorphism and liver cancer risk.

Tumor necrosis factor alpha (TNF-α) has been suggested to play an important role in the development and liver cancer. TNF-α 238 G/A polymorphism was hypothesized to increase the risk of liver cancer, but findings from previous studies were controversial. To explore a more precise estimation of the relationship between TNF-α 238 G/A polymorphism and liver cancer, we performed a meta-analysis. PubMed, Embase, and China Biology Medicine databases were searched for all publications on this association through March 12, 2013. Odds ratios (ORs) with its 95% confidence intervals (CIs) were used to assess the strength of this association. Eleven studies with 1,406 liver cancer cases and 2,386 noncancer controls were included into this meta-analysis. Overall, there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer under all three genetic models (A vs. G, OR 1.51, 95% CI 1.20-1.89, P < 0.001, I(2) = 37.7%; AG vs. GG, OR 1.49, 95% CI 1.01-2.21, P = 0.045, I(2) = 53.2%; AA/AG vs. GG, OR 1.76, 95% CI 1.35-2.30, P < 0.001, I(2) = 36.5%). The sensitivity analysis further strengthened the validity of the positive association. Subgroup analysis of nine studies from Asian countries showed that there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer in Asians (A vs. G, OR 1.35, 95% CI 1.03-1.76, P = 0.027, I(2) = 40.2%; AA/AG vs. GG, OR 1.56, 95% CI 1.14-2.15, P = 0.006, I(2) = 41.9%). In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of liver cancer, especially in Asians.