Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma
Introduction
In the recent 2001 Annual Report to the Nation on the Status of Cancer in the USA, primary liver cancer had the highest increase in incidence of all tumors during the past decade [1]. It is projected that the incidence of HCC in the US will continue to increase over the next 2 decades partially as a result of the hepatitis C (HCV) epidemic [2]. The most important and consistently identified risk factor for HCC is cirrhosis [3]. Worldwide, chronic HCV and hepatitis B (HBV) infection are the most important etiologic factors for the development of HCC [4]. It has been estimated that the lifetime risk of patients with HCV and HBV cirrhosis is between 10 and 37% [5], [6]. Therefore, not all cirrhotics and not all patients with chronic HCV or HBV infection will develop HCC. It is possible that environmental factors may play a role in determining which patients with cirrhosis develop HCC.
Alcohol has been previously studied as a risk factor for HCC. Heavy alcohol consumption has been shown to increase the risk of HCC compared to controls without liver disease [7]. The results of studies on tobacco as a risk factor for HCC have been conflicting, varying from no significant risk to a 3-fold increase compared to non-smokers [8], [9]. Obesity has been recently shown to be an important risk factor for liver cancer [10]. Diabetes has also been reported to be associated with an increase in risk of HCC [11].
There are significant limitations with available literature on the effects of alcohol and tobacco on the risk of HCC. First, the choice of controls is critical and should include individuals at risk of developing HCC [12]. Most studies evaluating risk factors for HCC employed controls without liver disease, who are at extremely low risk of developing HCC, and may have overestimated the impact of the risk factors studied. Secondly, most studies have been performed outside the US in which the cultural acceptance of tobacco and alcohol intake and the predominant etiology of the underlying liver disease may differ. Therefore, we performed a case-controlled study to test the hypothesis that tobacco, alcohol, and obesity independently increase the risk of HCC among Americans with cirrhosis.
Section snippets
Subjects
We conducted a prospective case-control study of 210 subjects enrolled from the Liver or General Medicine Clinics at our hospital. This study was approved by the University of Michigan Institutional Review Board, and informed consent was obtained from all participants. Treatment-naïve HCC patients were recruited between June 2002 and August 2003, only 7 HCC patients seen during this period refused enrollment. The diagnosis of HCC was made by histopathology (n=57), and if histopathology was not
Patient characteristics
There was no difference in age or gender among the three groups (Table 1). In addition, the patients with cirrhosis and HCC were comparable with regards to etiology of underlying liver disease and race. All HCC patients had cirrhosis based on histological (n=54) or laboratory and radiological (n=16) criteria. The mean Child-Turcotte-Pugh (CTP) and Model for Endstage Liver Disease (MELD) scores were similar among HCC and cirrhotic patients. There was no difference in the presence of ascites
Discussion
In this case-control study, we showed that alcohol consumption, tobacco smoking and obesity are independent risk factors of HCC. Compared to normal controls with no liver disease, alcohol, tobacco and obesity were associated with a 24-, 64-, and 48-fold increase in risk of HCC, respectively. The effects of these risk factors were less dramatic when HCC patients were compared to cirrhotic controls, but a statistically significant effect persisted indicating that these factors may play a role in
Acknowledgements
This work was supported by NIH CA 864000 Great Lakes New England Clinical Epidemiology Center of the Early Detection Research Network (JAM), and NIH DK064909 (JAM).
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