The Tumor Necrosis Factor-α-308 and -238 Polymorphisms and Risk of Hepatocellular Carcinoma for Asian Populations: A Meta-Analysis

BACKGROUND: Tumor necrosis factor-α (TNF-α) has been suggested to play a very important role in the development and progression of hepatocellular carcinoma (HCC). Many studies have identified the associations of TNF-α-308 and -238 polymorphisms with HCC risk, but the results remain controversial. AIM: We conducted this meta-analysis to evaluate the associations between TNF-α-308 and -238 polymorphisms and HCC susceptibility. METHODS: PubMed, Embase, and China National Knowledge Infrastructure electronic databases were searched for all articles on associations between TNF-α-308 and -238 polymorphisms and HCC risk in Asians through September 30, 2013. Odds ratios (ORs) and their 95% CIs were calculated to assess the strength of this association. RESULTS: A total of 17 case–control studies were identified in our meta-analysis. For the TNF-α-308 G/A polymorphism, 14 studies containing 3154 cases and 3767 controls were included. Overall, the frequency of the A allele was higher in patients with HCC than in the healthy controls (10.2% vs 7.5%), and the A allele and allele carrier were significantly associated with increased risk of HCC in a random effects model (A vs G: OR = 1.57; 95% CI, 1.22–2.01; P = 0.0004; AA + AG vs GG: OR = 1.62; 95% CI, 1.18–2.22; P = 0.003). For the TNF-α-238 polymorphism, 10 research articles were identified. No association was found between the TNF-α-238 G/A polymorphism and risk of HCC in any genetic models (P > 0.05). The sensitivity analysis further strengthened the overall correlations. CONCLUSIONS: Our meta-analysis proved that the TNF-α-308 G/A polymorphism is associated with increased susceptibility to HCC. However, the TNF-α-238 G/A polymorphism is not significantly associated with risk of HCC in Asian populations. Further studies with large sample sizes are needed to confirm these associations among other populations.