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Risk Factors for Hepatocellular Carcinoma in a Japanese Population: A Nested Case-Control Study

Departments of ¹ Clinical Studies, ² Statistics, and ³ Epidemiology, Radiation Effects Research Foundation; ⁴ Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; and ⁵ Department of Environmental Health, National Institute of Public Health, Wako, Japan

Requests for reprints: Waka Ohishi, Department of Clinical Studies, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. Phone: 81-82-261-3131; Fax: 81-82-261-3259. E-mail: nwaka{at}rerf.or.jp

Background: Epidemiologic studies have shown effects of lifestyle-related factors on risk for hepatocellular carcinoma. However, few cohort studies have incorporated, in a strict and in-depth manner, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections or investigated synergism between such factors.

Methods: We conducted a nested case-control study using sera stored before hepatocellular carcinoma diagnosis in the longitudinal cohort of atomic bomb survivors. The study included 224 hepatocellular carcinoma cases and 644 controls that were matched to the cases on gender, age, city, time of serum storage, and method of serum storage, and countermatched on radiation dose.

Results: Univariate analysis showed that HBV and HCV infections, alcohol consumption, smoking habit, body mass index (BMI), and diabetes mellitus were associated with increased hepatocellular carcinoma risk, whereas coffee drinking was associated with decreased hepatocellular carcinoma risk. Multivariate relative risks of hepatocellular carcinoma (95% confidence interval) were 45.8 (15.2-138), 101 (38.7-263), 70.7 (8.3-601), 4.36 (1.48-13.0), and 4.57 (1.85-11.3), for HBV infection alone, HCV infection alone, both HBV and HCV infections, alcohol consumption of 40 g of ethanol per day, and BMI of >25.0 kg/m² 10 years before diagnosis, respectively. HBV and HCV infection and BMI of >25.0 kg/m² remained independent risk factors even after adjusting for severity of liver fibrosis. Among HCV-infected individuals, the relative risk of hepatocellular carcinoma for a 1 kg/m² increase in BMI was 1.39 (P = 0.003).

Conclusions: To limit the risk for hepatocellular carcinoma, control of excess weight may be crucial for individuals with chronic liver disease, especially those with chronic hepatitis C. (Cancer Epidemiol Biomarkers Prev 2008;17(4):846–54)