AS296 - Cohort Consortium Study of Etiology of Hepatocellular Carcinoma in the United States

This page provides study documentation for AS296. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).‚Äč

Investigator Names and Contact Information

Katherine McGlynn, Ph.D., MPH []


Incidence and mortality rates of hepatocellular carcinoma (HCC) in the United States have been increasing since approximately 1980 in almost all segments of the population 1.  The etiology of HCC in the U.S., however, is not well elucidated.  An examination of known HCC risk factors in the SEER-Medicare linked databases found that only 52% of HCC could be explained by excessive alcohol consumption (16%), hepatitis C virus (HCV) infection (10%), hepatitis B virus (HBV) infection (5%), or some combination of the three factors (21%)2.  A small proportion (~5%) of HCC is linked to rare disorders such as hemochromatosis and a-1 antitrypsin deficiency.  The remaining 40-45% of HCC remains unexplained at the present time.  Thus, an examination of other factors might greatly enhance the current understanding of the etiology of HCC in the U.S. and help to explain why the incidence is now increasing.

Prior studies of HCC in the U.S. have been hampered by the rarity of the tumor.  In addition, most previous studies have employed a retrospective design, raising questions about the influence of recall bias.  The identification of risk factors through prospective analyses is needed, although it is difficult to assemble sufficient numbers of cases in any individual study.  A consortial approach has therefore been adopted, in which data from a number of studies will be pooled to derive sufficient power.  Cohorts with serum samples will be especially valuable in order to a analyses for the known HCC risk factors: HBV and HCV infection.  Questionnaire data and serum samples are being sought from all U.S. studies in the NCI Cohort Consortium for this effort.

Specific Aims

1) Using questionnaire data, conduct pooled analyses to assess the extent to which HCC risk is influenced by a number of factors including: diabetes and diabetes medications, obesity, physical inactivity, cigarette smoking; alcohol consumption, reproductive history, hormonal exposures, usage of NSAIDs and statins, dietary factors, including coffee consumption, and other putative risk factors.
2) Using serum samples from some Cohort Consortium studies, HBV and HCV infection status will be determined in order to account for these known HCC risk factors.


1. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005. J Clin Oncol 2009.
2. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology 2004;127(5):1372-80.