Background: Hepatocellular carcinoma (HCC) is one of the few cancers with an increasing incidence and mortality worldwide. This study aims to determine the contribution of known risk factors for HCC by race and ethnicity.
Methods: Data on race, ethnicity, age, and gender were obtained from National Health and Nutrition Examination Survey (NHANES). Population attributable fractions (PAFs) of risk factors were estimated using non-invasive scoring measures of Hepatitis B and C virus infection, excessive alcohol use, smoking, diabetes and emerging metabolic risk factors [non-alcoholic steatohepatitis advanced cirrhosis (NASH) and non-alcoholic fatty liver disease-advanced fibrosis (NAFLD-fib)] over a 10-year period, 1999-2002 and 2009-2012. Genetic analysis was performed using DisGenet platform by attaining the top enriched genes strongly related to HCC. Furthermore, cytoscape network was used to form a gene-disease network association.
Results: NASH-cirrhosis increased in the overall population and among all race and ethnic groups. Both liver fat accumulation and ALT levels vary among different populations; however, Hispanics have the highest prevalence of NAFLD and elevated ALT levels. Non-Hispanic (NH) blacks and Hispanics had a 3 to 4 times higher PAF for HCC than whites attributed due to chronic liver diseases, including NASH-cirrhosis and NAFLD-fib. Our genetic analysis demonstrated that PNPLA3 polymorphism is strongly associated with NAFLD-fib, which appears to represent susceptibility to liver disease among the Hispanic community.
Conclusion: Hispanics and NH blacks are at a disproportionately higher risk for HCC in part due to the higher prevalence of liver disease comorbidities, including NASH-cirrhosis and NAFLD-fib. Compared to NH whites, Hispanics and NH blacks have a higher baseline risk for liver cancer due to non-metabolic factors, which may include a genetic susceptibility. Metabolic risk factors have increased and are now contributing to nearly half of HCC cases in the US.