학술논문

Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank
Document Type
article
Source
British Journal of Cancer. 123(2)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Liver Disease
Cancer
Digestive Diseases
Contraception/Reproduction
Clinical Research
Digestive Diseases - (Gallbladder)
Liver Cancer
Prevention
Rare Diseases
Aetiology
2.1 Biological and endogenous factors
Reproductive health and childbirth
Good Health and Well Being
Aged
Bile Ducts
Bile Ducts
Intrahepatic
Biological Specimen Banks
Cholangiocarcinoma
Cohort Studies
Contraceptives
Oral
Hormonal
Estrogen Receptor alpha
Estrogen Receptor beta
Female
Gene Expression Regulation
Neoplastic
Hormones
Humans
Hysterectomy
Liver Neoplasms
Menopause
Middle Aged
Proportional Hazards Models
Risk Factors
United Kingdom
Public Health and Health Services
Oncology & Carcinogenesis
Oncology and carcinogenesis
Language
Abstract
BackgroundIntrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.MethodsWe harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases).ResultsHysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.ConclusionsThis study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.