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.