Petrick JL1,2, McMenamin ÚC3, Zhang X4, Zeleniuch-Jacquotte A5,6, Wactawski-Wende J7, Simon TG8, Sinha R9, Sesso HD10,11, Schairer C9, Rosenberg L12, Rohan TE13, Robien K14, Purdue MP9, Poynter JN15, Palmer JR12, Lu Y16, Linet MS9, Liao LM9, Lee IM10,11, Koshiol J9, Kitahara CM9, Kirsh VA17, Hofmann JN9, Graubard BI9, Giovannucci E10, Gaziano JM11,18, Gapstur SM19, Freedman ND9, Florio AA9, Chong DQ20, Chen Y5,21, Chan AT4,8,22, Buring JE10,11, Freeman LEB9, Bea JW23, Cardwell CR3, Campbell PT19, McGlynn KA9.
Br J Cancer. 2020 May 7. doi: 10.1038/s41416-020-0835-5. [Epub ahead of print]
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.
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).
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.
This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.