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.

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.

• Authors: Jessica L Petrick, Úna C McMenamin, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Tracey G Simon, Rashmi Sinha, Howard D Sesso, Catherine Schairer, Lynn Rosenberg, Thomas E Rohan, Kim Robien, Mark P Purdue, Jenny N Poynter, Julie R Palmer, Yunxia Lu, Martha S Linet, Linda M Liao, I-Min Lee, Jill Koshiol, Cari M Kitahara, Victoria A Kirsh, Jonathan N Hofmann, Barry I Graubard, Edward Giovannucci, J Michael Gaziano, Susan M Gapstur, Neal D Freedman, Andrea A Florio, Dawn Q Chong, Yu Chen, Andrew T Chan, Julie E Buring, Laura E Beane Freeman, Jennifer W Bea, Christopher R Cardwell, Peter T Campbell, Katherine A McGlynn
• Journal: British journal of cancer (Br J Cancer) Vol. 123 Issue 2 Pg. 316-324 (07 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 32376888 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Contraceptives, Oral, Hormonal
• ESR1 protein, human
• ESR2 protein, human
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Hormones

Topics

• Aged
• Bile Ducts
• Bile Ducts, Intrahepatic
• Biological Specimen Banks
• Cholangiocarcinoma (chemically induced, epidemiology, metabolism, 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, therapeutic use)
• Humans
• Hysterectomy (adverse effects)
• Liver Neoplasms (chemically induced, epidemiology, metabolism, pathology)
• Menopause (drug effects)
• Middle Aged
• Proportional Hazards Models
• Risk Factors
• United Kingdom (epidemiology)