{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:21:01Z","timestamp":1787239261273,"version":"build-2736575974"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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-\u03b1 and -\u03b2, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\u20131998 and 2006\u20132010, 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\u00a0LCPP (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009180 cases) and the UK Biobank (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200957 cases).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hysterectomy was associated with a doubling of ICC risk (HR\u2009=\u20091.98,\u00a095%\u00a0CI:\u00a01.27\u20133.09), compared to women aged 50\u201354 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR\u2009=\u20091.62,\u00a095%\u00a0CI:\u00a01.03\u20132.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-020-0835-5","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T19:04:36Z","timestamp":1588791876000},"page":"316-324","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"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\u00a0UK Biobank"],"prefix":"10.1038","volume":"123","author":[{"given":"Jessica L.","family":"Petrick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dana C.","family":"McMenamin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Zeleniuch-Jacquotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Wactawski-Wende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey G.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard D.","family":"Sesso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Schairer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Rohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Robien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Purdue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny N.","family":"Poynter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha S.","family":"Linet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Koshiol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cari M.","family":"Kitahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Kirsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan N.","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry I.","family":"Graubard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Giovannucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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The UK Biobank was approved by the North West Multi-Centre Research Ethics Committee. All participants provided written informed consent, and the study was performed in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Data can be obtained for legitimate research purposes. Access to LCPP data can be provided by submitting a request to Katherine McGlynn (mcglynnk@mail.nih.gov) or Peter Campbell (peter.campbell@cancer.org). UK Biobank data can be provided by submitting an application to the UK Biobank (\n                      \n                      ).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship (\u00da.C.M.). NIH Intramural Research Program, National Cancer Institute (J.L.P., A.A.F., L.E.B.F., J.N.H., C.M.K., N.D.F., B.I.G., J.K., L.M.L., M.S.L., M.P.P., C.S., R.S., K.A.M.). National Institutes of Health grants CA047988 (I.L., J.E.B.), CA182913 (I.L., J.E.B.), HL043851 (I.L., J.E.B.), HL080467 (I.L., J.E.B.), HL099355 (I.L., J.E.B.), K07 CA188126 (X.Z.), DK098311 (A.T.C.), CA186107 (A.T.C.), CA87969 (A.T.C.), CA167552 (A.T.C.), P30 CA016087 (A.Z-J.), P30 ES000260 (A.Z-J.), UM1 CA164974 (L Rosenberg, JR Palmer), R01 CA058420 (L.R., J.R.P.), and R01 CA39742 (K.R., J.N.P.). American Cancer Society Research Scholar Grant RSG NEC-130476 (X.Z.). The WHI program (J.W-W., T.E.R., Y.L., J.W.B.) is funded by the National Institutes of Health contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C and HHSN268201600004C. The HPFS and NHS programs (X.Z.) were support by the National Cancer Institute, National Institutes of Health grant numbers UM1CA186107, P50CA127003, P01CA87969 and UM1CA167552.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding infromation"}}]}}