Association between PNPLA3 rs738409 polymorphism and hepatocellular carcinoma risk: an updated meta-analysis

Hepatocellular carcinoma (HCC) is a common malignant tumor and the leading cause of cancer-related death worldwide. The protein encoded by patatin-like phospholipase domain-containing protein 3 (PNPLA3) plays important roles in liver fatty metabolism. Recent studies have indicated associations of PNPLA3 rs738409 with various liver diseases, including HCC. This meta-analysis was performed to investigate and update the association between rs738409 polymorphism and the risk of HCC, and to test the association between rs738409 and HCC specifically in patients within chronic hepatitis B and/or C infection, alcoholic liver disease, or other diseases. Studies were searched from the literature database up to March 31, 2016. The meta-analysis was conducted based on statement of preferred reporting items for systematic reviews and meta-analyses. Pooled odds ratios (OR) and 95 % confidence intervals (CI) were estimated the strength of associations between rs738409 polymorphism and HCC risk. Fifteen published studies, consisting of 2264 HCC patients (case) and 5802 without HCC individuals (control), were included in the present study. Meta-analysis revealed that rs738409 polymorphism contributed to HCC risk under the allelic effect model (C vs. G: OR 1.73; 95 % CI 1.53-1.96), the dominant effect model (CC vs. CG+GG: OR 1.61; 95 % CI 1.44-1.81), and the recessive effect model (CC+CG vs. GG: OR 2.66; 95 % CI 2.28-3.11). Furthermore, the effect of rs738409 G allele on liver oncogenesis was higher in alcoholic liver disease (OR 2.55), compared to chronic hepatitis C/B (OR 1.32) and other diseases (OR 2.27). The results suggested that rs738409 polymorphism was significantly associated with HCC risk and it could be used as one risk factor for HCC.