PNPLA3 Gene Polymorphism and Liver- and Extrahepatic Cancer-Related Mortality in the United States

The palatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 G allele is associated with nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma,1 and all-cause or cardiovascular mortality in the general population.2 One recent Italian study reported an association between PNPLA3 polymorphism and liver related events and mortality in biopsy-confirmed NAFLD.3 Regarding extrahepatic cancer?related mortality, one study showed that only women carrying the G allele without hepatic steatosis had a 60% lower risk for cancer-related mortality.4 However, owing to insufficient follow-up and selected populations, the results from these studies cannot generalize about the association between PNPLA3 polymorphism and liver-and extrahepatic cancer?related mortality at a population level. Thus, we investigated the association between PNPLA3 polymorphism and liver-and extrahepatic cancer?related mortality based on the presence of NAFLD in the U.S. general population.

Automated summary

The PNPLA3 rs738409 G allele is associated with NAFLD, hepatocellular carcinoma, and overall or cardiovascular mortality. Studies show that women carrying the G allele without hepatic steatosis have a 60% lower risk for cancer-related mortality.