Exogenous Hormone Use, Reproductive Factors and Risk of Intrahepatic Cholangiocarcinoma among Women: Results from Cohort Studies in the Liver Cancer Pooling Project and UK Biobank

Jessica Petrick, Úna 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, I-Min Lee, Jill Koshiol, Cari M. KitaharaVictoria A. Kirsh, Jonathan N. Hoffman, 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

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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 estrogen receptor-α and -β, and estrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating estradiol is associated with increased ICC risk, further supporting a hormonal etiology. 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 harmonized data from 1,107,498 women who enrolled 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 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.
Original languageEnglish
Number of pages9
JournalBritish Journal of Cancer
Early online date07 May 2020
Publication statusEarly online date - 07 May 2020

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    Petrick, J., McMenamin, Ú., Zhang, X., Zeleniuch-Jacquotte, A., Wactawski-Wende, J., Simon, T. G., Sinha, R., Sesso, H. D., Schairer, C., Rosenberg, L., Rohan, T. E., Robien, K., Purdue, M. P., Poynter, J. N., Palmer, J. R., Lu, Y., Linet, M. S., Lee, I-M., Koshiol, J., ... McGlynn, K. A. (2020). Exogenous Hormone Use, Reproductive Factors and Risk of Intrahepatic Cholangiocarcinoma among Women: Results from Cohort Studies in the Liver Cancer Pooling Project and UK Biobank. British Journal of Cancer.