title: Role of reproductive factors in hepatocellular carcinoma: Impact on hepatitis B- and C-related risk.
abstract: Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Estrogen may play some role in the development of HCC. We conducted a multicenter case-control study to evaluate the effects of reproductive factors on HCC risk, and to assess whether the association between each factor and HCC differs between hepatitis B surface antigen (HBsAg)-positive and -negative women, in which hepatitis C virus (HCV) is the major cause of HCC. The study included 218 women with HCC and 729 control women selected from nonbiological and first-degree female relatives of patients with HCC. The risk of HCC was inversely related to the number of full-term pregnancies (FTP) (P(trend) =.0216) and age at natural menopause (P(trend) =.0251 among women aged 45-55 without prior surgical menopause). Oophorectomy at age <or=50 during premenopausal years was also a risk factor (multivariate-adjusted OR, 2.57; 95% CI, 1.42-4.63). Use of hormone replacement therapy (HRT) (multivariate-adjusted OR, 0.46; 95% CI, 0.27-0.79) was associated with a lower risk of HCC, and there was a trend in the risk with increasing duration of HRT (P(trend) = 0.0013). All reproductive factors had a similar impact on HBsAg-positive and -negative women except for an early menarche (<or=12 vs. >or=16 years), which increased HCC risk in HBsAg carriers (multivariate-adjusted OR, 6.96; 95% CI, 2.52-19.18) but posed no increased risk in noncarriers (P(interaction) =.0053). In conclusion, increased exposure to estrogen during adulthood may provide a protective effect against HCC. Nevertheless, an early menarche, which results in early estrogen exposure, does not confer protection for HBsAg carriers.
authors.affiliation: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. mingwhei@ha.mc.ntu.edu
authors.forename: Ming-Whei
authors.initials: MW
authors.lastname: Yu
authors.forename: Hung-Chuen
authors.initials: HC
authors.lastname: Chang
authors.forename: Shun-Chiao
authors.initials: SC
authors.lastname: Chang
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Shee-Chan
authors.initials: SC
authors.lastname: Lin
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects; D015914:Estrogen Replacement Therapy; D005260:Female; D006509:Hepatitis B / Q000209:etiology*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006526:Hepatitis C / Q000209:etiology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008593:Menopause; D008875:Middle Aged; D010052:Ovariectomy / Q000009:adverse effects; D012098:Reproduction; D012306:Risk
chemical_list: D003276:Contraceptives, Oral; D006514:Hepatitis B Surface Antigens