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Population-Attributable Fractions of Risk Factors for Hepatocellular Carcinoma in the United States

Welzel, Tania M MD1; Graubard, Barry I PhD2; Quraishi, Sabah MPH2; Zeuzem, Stefan MD1; Davila, Jessica A PhD3, 4; El-Serag, Hashem B MD3, 4; McGlynn, Katherine A PhD2

American Journal of Gastroenterology: August 2013 - Volume 108 - Issue 8 - p 1314–1321
doi: 10.1038/ajg.2013.160

OBJECTIVES: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.

METHODS: Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.

RESULTS: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29–43.84), HBV (OR 11.17, 95% CI: 9.18–13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82–4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97–4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34–2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).

CONCLUSIONS: The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.

1 Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany

2 Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, USA

3 Houston Veterans Affairs Medical Center, Houston, Texas, USA

4 Baylor College of Medicine, Houston, Texas, USA

Correspondence: Katherine A. McGlynn, PhD, DCEG, NCI, NIH, EPS-5022, 6120 Executive Boulevard, Rockville, Maryland 20852, USA. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 9 January 2013; accepted 28 April 2013

published online 11 June 2013

© The American College of Gastroenterology 2013. All Rights Reserved.
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