Title: 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.
Authors: Petrick, Jessica L; McMenamin, Úna C; Zhang, Xuehong; Zeleniuch-Jacquotte, Anne; Wactawski-Wende, Jean; Simon, Tracey G; Sinha, Rashmi; Sesso, Howard D; Schairer, Catherine; Rosenberg, Lynn; Rohan, Thomas E; Robien, Kim; Purdue, Mark P; Poynter, Jenny N; Palmer, Julie R; Lu, Yunxia; Linet, Martha S; Liao, Linda M; Lee, I-Min; Koshiol, Jill; Kitahara, Cari M; Kirsh, Victoria A; Hofmann, Jonathan N; Graubard, Barry I; Giovannucci, Edward; Gaziano, J Michael; Gapstur, Susan M; Freedman, Neal D; Florio, Andrea A; Chong, Dawn Q; Chen, Yu; Chan, Andrew T; Buring, Julie E; Freeman, Laura E Beane; Bea, Jennifer W; Cardwell, Christopher R; Campbell, Peter T; McGlynn, Katherine A
Published In Br J Cancer, (2020 07)
Abstract: BACKGROUND: Intrahepatic 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. METHODS: We 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). RESULTS: Hysterectomy 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. CONCLUSIONS: This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.
PubMed ID: 32376888
MeSH Terms: Aged; Bile Ducts; Bile Ducts, Intrahepatic; Biological Specimen Banks; Cholangiocarcinoma/chemically induced; Cholangiocarcinoma/epidemiology*; Cholangiocarcinoma/metabolism; Cholangiocarcinoma/pathology; Cohort Studies; Contraceptives, Oral, Hormonal/adverse effects*; Estrogen Receptor alpha/genetics; Estrogen Receptor beta/genetics; Female; Gene Expression Regulation, Neoplastic/drug effects; Hormones/adverse effects*; Hormones/therapeutic use; Humans; Hysterectomy/adverse effects; Liver Neoplasms/chemically induced; Liver Neoplasms/epidemiology*; Liver Neoplasms/metabolism; Liver Neoplasms/pathology; Menopause/drug effects; Middle Aged; Proportional Hazards Models; Risk Factors; United Kingdom/epidemiology