Association Between the Risk of Hepatitis Virus-Related Hepatocellular Carcinoma and EGF Polymorphism: An Updated Meta-Analysis

Background: The study aims to provide a comprehensive account of the association of the EGF 61A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC). Methods Electronic searches of the Chinese National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journal Database (VIP), PubMed, Web of Science, and Embase were systematically conducted to select studies by two independent researchers. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to assess the strength of the association. Results In general, a total of 18 articles were enrolled with 2692 cases and 5835 controls for rs4444903. The meta-analysis results of the pooling all studies showed that the EGF + 61A/G polymorphism was significantly associated with an increased risk of virus-related hepatocellular carcinoma in all genetic models. In subgroup analyzes based upon ethnicity, a significantly elevated association was observed between EGF + 61A/G polymorphism and the risk of virus-related hepatocellular carcinoma in Asian populations (G vs. A: OR = 1.15, P < 0.001, 95% CI: 1.02–1.29, I 2  = 40.1%), European populations (G vs. A: OR = 1.59, P < 0.001, 95% CI: 1.05–2.41, I 2  = 0.0%) and African populations (G vs. A: OR = 4.46, P < 0.001, 95% CI 1.53–13.02, I 2  = 93%) Conclusions EGF gene + 61A/G polymorphism is significantly associated with the increased risk of HCC, particularly in Asian populations.