Population attributable fractions of risk factors for hepatocellular carcinoma in the United States

Cancer. 2016 Jun 1;122(11):1757-65. doi: 10.1002/cncr.29971. Epub 2016 Mar 21.


Background: Hepatocellular carcinoma (HCC) incidence has been increasing in the United States for several decades; and, as the incidence of hepatitis C virus (HCV) infection declines and the prevalence of metabolic disorders rises, the proportion of HCC attributable to various risk factors may be changing.

Methods: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage were used to calculate population attributable fractions (PAFs) for each risk factor over time. Patients with HCC (n = 10,708) who were diagnosed during the years 2000 through 2011 were compared with a 5% random sample of cancer-free controls (n = 332,107) residing in the Surveillance, Epidemiology, and End Results areas. Adjusted odds ratios (ORs) and PAFs were calculated for HCV, hepatitis B virus (HBV), metabolic disorders, alcohol-related disorders, smoking, and genetic disorders.

Results: Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%; 95% confidence interval [CI], 31.9%-46.7%) and whites (PAF, 34.8%; 95% CI, 33.1%-36.5%), whereas HCV had the largest PAF among blacks (PAF, 36.1%; 95% CI, 31.8%-40.4%) and Asians (PAF, 29.7%; 95% CI, 25.9%-33.4%). Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% (95% CI, 22.8%-28.9%) to 36% (95% CI, 33.6%-38.5%). In contrast, the PAFs of alcohol-related disorders and HCV remained stable.

Conclusions: Among US Medicare recipients, metabolic disorders contribute more to the burden of HCC than any other risk factor, and the fraction of HCC caused by metabolic disorders has increased in the last decade. Cancer 2016;122:1757-65. Published 2016. This article is a U.S. Government work and is in the public domain in the USA..

Keywords: attributable fractions; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; metabolic disorders; population.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Alcohol Drinking / adverse effects
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Ethnicity
  • Female
  • Genetic Diseases, Inborn / complications
  • Hepatitis B / complications
  • Hepatitis C / complications
  • Humans
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology*
  • Male
  • Metabolic Diseases / complications
  • Odds Ratio
  • Risk Factors
  • SEER Program
  • Sex Factors
  • Smoking / adverse effects