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.
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 language | English |
|---|---|
| Number of pages | 9 |
| Journal | British Journal of Cancer |
| Early online date | 07 May 2020 |
| Publication status | Early online date - 07 May 2020 |
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- 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
© 2020 The Authors. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
- 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
© 2020 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.