Correlation between PNPLA3 rs738409 polymorphism and hepatocellular carcinoma: a meta-analysis of 10,330 subjects

Purpose: The correlation between patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism and hepatocellular carcinoma was investigated by several pilot studies, but the results of these studies were controversial. Therefore, we performed this study to better assess the relationship between PNPLA3 rs738409 polymorphism and the likelihood of hepatocellular carcinoma. Methods: Eligible studies were searched in PubMed, Medline, EMBASE, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between PNPLA3 rs738409 polymorphism and hepatocellular carcinoma. Results: A total of 17 studies with 10,330 participants were analyzed. A significant association with the likelihood of hepatocellular carcinoma was detected for the PNPLA3 rs738409 polymorphism in dominant (P = 0.0001; OR 0.66; 95% CI 0.53, 0.82), recessive (P < 0.0001; OR 2.32; 95% CI 1.76, 3.06) and allele (P < 0.0001; OR 0.64; 95% CI 0.53, 0.77) comparisons. Further subgroup analyses revealed that the PNPLA3 rs738409 polymorphism was significantly associated with the likelihood of hepatocellular carcinoma in Caucasians (dominant model: P < 0.0001, OR 0.57, 95% CI 0.45, 0.71; recessive model: P < 0.0001, OR 2.74, 95% CI 2.02, 3.71; allele model: P < 0.0001, OR 0.56, 95% CI 0.46, 0.67). However, no positive results were detected in Asians. Conclusions: Our findings indicated that the PNPLA3 rs738409 polymorphism may serve as a potential biological marker of hepatocellular carcinoma in Caucasians.