Risk Factors for Hepatocellular Carcinoma of Women in Taiwan

Objective: Hepatocellular carcinoma (HCC) is a leading malignant neoplasm with an extraordinarily high fatality. It is the first leading cancer death in men and the second leading cancer death in women in Taiwan. Most previous cohort studies on HCC risk factor were focused on males. This long-term follow-up study on a large female cohort aimed to analyze HCC risk factors including virus infection, lifestyle factors, obesity, familial disease history, and reproductive factors.

Methods: From 1991 to 1992, we enrolled 11920 women with ages between 30 and 65 years from seven townships in Taiwan. Lifestyle and reproductive risk factors were collected at recruitment through a standardized personal interview based on a structured questionnaire. Blood samples collected at cohort entry were tested for HBsAg and HBeAg by radioimmunoassay, HBV DNA by polymerase chain reaction, anti-HCV by enzyme immunoassay, and HPV genotyping by genechip hybridization. The relationship of potential risk factors measured at study entry was analyzed using Cox proportional hazards model.

Results: There were 71 newly-diagnosed HCC cases during 136,575 person-years of follow-up. The HCC incidence rate was 52 per 100.000 person-years. The relative risk (RR) of developing HCC was 2.8 (95% confidence interval, CI: 1.5-5.2) among women who were only HBsAg seropositive, and 15.5 (95%CI: 7.5-31.9) among those who were seropositive for both HBsAg and HBeAg in comparison with those who were seronegative on HBsAg and HBeAg. The RR of developing HCC for a serum HBV DNA level >105 copies/mL was 9.0 (95%CI: 3.1-26.4). In the multivariate analysis, statistically significant HCC risk factors other than viral infection included cigarette smoking, early menopause (<50 years), obesity, and family history of liver cirrhosis and HCC. In the analysis of interaction between HBV and HCV chronic infection, there was no synergistic effect. In the subcohort analysis of association between HCC and HPV, the RR (95% CI) were 4.5 (1.7-11.8), 1.3 (0.3-5.7), 14.1 (3.9-51.5), respectively, for only HBsAg-seropositive, only HPV DNA positive, and both positive in comparison with those without both infections.

Conclusion: In Taiwan, an area endemic of chronic hepatitis virus infection, both HBV and HCV were playing a major role in the development of HCC. Cigarette smoking, early menopause and obesity were also important HCC risk factors.