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Risk factors for hepatocellular carcinoma in the United States

Principal Investigator
Name
Katherine McGlynn
Institution
NCI, DCEG, HREB
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2009-0154
Initial CDAS Request Approval
Jul 23, 2009
Title
Risk factors for hepatocellular carcinoma in the United States
Summary
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). Reasons for the increase are unclear, although much speculation has focused on the role of chronic hepatitis C virus (HCV) infection (2). While HCV is certainly a risk factor for HCC in the U.S., other known and putative factors may also be contributing to the increase in incidence. The etiology of HCC in the U.S., however, is not well understood. An examination of known HCC risk factors in the SEER-Medicare linked databases found that only 52% of HCC could be explained by alcohol consumption (16%), HCV infection (10%), hepatitis B virus (HBV) infection (5%), or some combination of the three factors (21%) (3). A small proportion (~5%) of HCC is linked to rare disorders such as hemochromatosis and a-1 antitrysin deficiency. The remaining 40-45% of HCC remains unexplained at the current 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.
Aims

1). Diabetes, diabetes medications, obesity and development of HCC. We propose to examine whether preexisting diabetes and obesity increase the risk of developing HCC. The factors will be examined together and separately. We also propose to examine whether diabetic medications affect any risk associated with diabetes. 2). Reproductive factors in women and risk of HCC. We propose to examine whether the risk of HCC is women is altered by reproductive events such as age at first birth, parity, age at menarche, age at menopause and age at last birth are related to risk. If a sufficient number of women are exposed, we also propose to examine whether oral contraceptive use and/or hormone replacement therapy use are related to risk of HCC. 3). Use of non-steroidal anti-inflammatory drugs (NSAIDs), statins and HCC. Inflammation is a hallmark of HCC, thus NSAID use may be inversely related to risk. Use of cholesterol-lowering statins (3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors) has been suggested to be inversely related to the development of HCC, though few studies have directly examined the hypothesis. We propose to examine the relationship between both medications and development of HCC. 4). Dietary factors and HCC Folate intake and consumption of coffee have been associated with reduced risk of HCC in some case-control studies. Whether consumption of either item was accurately captured retrospectively, however, is uncertain. We propose to examine both dietary items and risk of HCC.

Collaborators

Ellen Chang (Stanford University School of Medicine)
Neal Freedman (DCEG/NEB)
Barry Graubard (DCEG/BB)
Allan Hildesheim (DCEG/IIB)
Ann Hsing (DCEG/HREB)