Abstract
Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25–2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06–1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04–1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09–1.31) and EHBDC (HR 1.11; 95% CI 1.01–1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 863-872 |
| Number of pages | 10 |
| Journal | Journal of Hepatology |
| Volume | 73 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2020 |
Keywords
- Biliary tract cancer
- Gallbladder cancer
- Parity
- Reproductive factors
ASJC Scopus subject areas
- Hepatology
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Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project. / Jackson, Sarah S.; Adami, Hans Olov; Andreotti, Gabriella et al.
In: Journal of Hepatology, Vol. 73, No. 4, 10.2020, p. 863-872.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project
AU - Jackson, Sarah S.
AU - Adami, Hans Olov
AU - Andreotti, Gabriella
AU - Beane-Freeman, Laura E.
AU - de González, Amy Berrington
AU - Buring, Julie E.
AU - Fraser, Gary E.
AU - Freedman, Neal D.
AU - Gapstur, Susan M.
AU - Gierach, Gretchen
AU - Giles, Graham G.
AU - Grodstein, Francine
AU - Hartge, Patricia
AU - Jenab, Mazda
AU - Kirsh, Victoria
AU - Knutsen, Synnove F.
AU - Lan, Qing
AU - Larsson, Susanna C.
AU - Lee, I. Min
AU - Lee, Mei Hsuan
AU - Liao, Linda M.
AU - Milne, Roger L.
AU - Monroe, Kristine R.
AU - Neuhouser, Marian L.
AU - O'Brien, Katie M.
AU - Petrick, Jessica L.
AU - Purdue, Mark P.
AU - Rohan, Thomas E.
AU - Sandin, Sven
AU - Sandler, Dale P.
AU - Sawada, Norie
AU - Shadyab, Aladdin H.
AU - Simon, Tracey G.
AU - Sinha, Rashmi
AU - Stolzenberg-Solomon, Rachael
AU - Tsugane, Shoichiro
AU - Weiderpass, Elisabete
AU - Wolk, Alicja
AU - Yang, Hwai I.
AU - Zheng, Wei
AU - McGlynn, Katherine A.
AU - Campbell, Peter T.
AU - Koshiol, Jill
N1 - Funding Information: BiTCaPP: This cohort consortium was funded by the Intramural Program of the National Institutes of Health , National Cancer Institute ( ZIA CP010218-01 ). AgHealth: This study was funded by the Intramural Program of the National Institutes of Health , National Cancer Institute ( Z01 P010119 ) and the National Institute of Environmental Health Sciences ( Z01 ES 049030-11 ). AHS-2: Project support was obtained from National Cancer Institute grant 1U01CA152939 and World Cancer Research Fund International (UK) grant 2009/93 . BCDDP : The BCDDP Follow-up Study was supported by the Intramural Research Program of the National Institutes of Health , National Cancer Institute . CPS-II NC : The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II Nutrition Cohort. CSP : This work was supported by Academia Sinica [ AS-TP-108-L09-3 ; AS-SUMMIT-108 ] and Ministry of Science and Technology [ 108-2314-B-001-008 ; 107-0210-01-19-01 ]. EPIC : The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by Danish Cancer Society , Denmark; Ligue Contre le Cancer , France; Institut Gustave Roussy , France; Mutuelle Generale de l'Education Nationale , France; Institut National de la Sante et de la Recherche Medicale , France; Deutsche Krebshilfe , Germany, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research , Germany; Hellenic Health Foundation , Greece; Italian Association for Research on Cancer ; National Research Council , Italy; Dutch Ministry of Public Health, Welfare and Sports , the Netherlands; Netherlands Cancer Registry , the Netherlands; LK Research Funds , the Netherlands; Dutch Prevention Funds , the Netherlands; Dutch ZON (Zorg Onderzoek Nederland), the Netherlands; World Cancer Research Fund , London, UK; Statistics Netherlands , the Netherlands; European Research Council , Norway; Health Research Fund , Regional Governments of Andalucia, Asturias, Basque Country, Murcia (project no. 6236 ) and Navarra , ISCIII RETIC ( RD06/0020/0091 ), Spain; Swedish Cancer Society , Sweden; Swedish Scientific Council , Sweden; Regional Government of Skane and Vasterbotten , Sweden; Cancer Research United Kingdom ; Medical Research Council , United Kingdom; Stroke Association , United Kingdom, British Heart Foundation , United Kingdom; Department of Health, Food Standards Agency , United Kingdom; and Wellcome Trust ; United Kingdom. We thank Bertrand Hemon for his precious help with the EPIC database. The principle investigators and funders corresponding to each of the EPIC centers that contributed cases were Kim Overvad, Anne Tjonneland (Denmark); Francoise Clavel-Chapelon (France); Heiner Boeing, Rudolf Kaaks (Germany); Antonia Trichopoulou (Greece); Vittorio Krogh, Domenico Palli, Paolo Vineis, Salvatore Panico, Rosario Tumino (Italy); Eiliv Lund (Norway); Antonio Agudo, Maria Jose Sanchez, J.Ramón Quirós, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro (Spain); Mattias Johansson, Jonas Manjer (Sweden); H. Bas Bueno-de-Mesquita, Petra H. Peeters (The Netherlands); Timothy Key, Nick Wareham (UK); The coordination of European Prospective Investigation into Cancer and Nutrition is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by the French National Cancer Institute (L'Institut National du Cancer; INCA); Ligue contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid ; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research ; Danish Cancer Society ; Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC) ( DR06/0020/0091 ); the participating regional governments from Asturias, Andalucía, Murcia, Navarra and Vasco Country and the Catalan Institute of Oncology of Spain ; Cancer Research UK ; Medical Research Council , UK; the Stroke Association , UK; British Heart Foundation ; Department of Health , UK; Food Standards Agency , UK; the Wellcome Trust , UK; the Hellenic Health Foundation ; Italian Association for Research on Cancer ; Compagnia San Paolo , Italy; Dutch Ministry of Public Health, Welfare and Sports ; Dutch Ministry of Health ; Dutch Prevention Funds ; LK Research Funds ; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Society ; Swedish Scientific Council ; Regional Government of Skane , Sweden; Nordforsk—Centre of Excellence programme . JPHC: This work was supported by the National Cancer Center Research and Development Fund (since 2011) and a grant-in-aid from Cancer Research (1989–2010) from the Ministry of Health, Labor, and Welfare of Japan . MCCS : MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria . The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057 , 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria . MEC: This work was supported by the National Institutes of Health ( P01 CA33619 and U01 CA164973 ). NHS : Data used in this study was supported by an Infrastructure Grant ( UM1 CA186107 ) and a program project grant that funds Cancer Research ( P01 CA87969 ). NHS would like to thank the participants and staff of the NHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. NIH-AARP : This research was supported [in part] by the Intramural Research Program of the NIH , National Cancer Institute . Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. Cancer incidence data from California were collected by the California Cancer Registry, California Department of Public Health's Cancer Surveillance and Research Branch, Sacramento, California. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, Lansing, Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (Miami, Florida) under contract with the Florida Department of Health, Tallahassee, Florida. The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Health Sciences Center School of Public Health, New Orleans, Louisiana. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, The Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry, Raleigh, North Carolina. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services, Phoenix, Arizona. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Division of Public and Behavioral Health, State of Nevada Department of Health and Human Services, Carson City, Nevada. PLCO : The PLCO Cancer Screening Trial is supported by contracts from the National Cancer Institute . SISTER : The Sister Study is supported by the Intramural Research Program of the National Institutes of Health , National Institute of Environmental Health Sciences ( ZO1-ES-044005 ). Support for data collection and study and data management are provided by Social & Scientific Systems, Inc. , and Westat, Inc. , Durham, NC. SMC : This cohort is supported by the Swedish Research Council (Research Infrastructure SIMPLER, 2017-00644 ), the Swedish Cancer Foundation , and by Strategic Funds from Karolinska Institutet , Stockholm, Sweden. SWHS : This project was supported by grants from the U.S. National Institutes of Health ( R37 CA070867 to W.Z., and R01 CA082729 and UM1 CA173640 to X.-O.S.) and by the Intramural Research Program (contract N02 CP1101066 ). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute , National Institutes of Health , U.S. Department of Health and Human Services through contracts, HHSN268201600018C , HHSN268201600001C , HHSN268201600002C , HHSN268201600003C , and HHSN268201600004C . WHS : WHS was supported by grants CA047988, CA182913, HL043851, HL080467, and HL099355. WLHS : The WLHS project was supported by the Swedish Research Council (grant number 521-2011-295 ) and a Distinguished Professor Award at Karolinska Institutet to Hans-Olov Adami, grant number: 2368/10-221 . Publisher Copyright: © 2020
PY - 2020/10
Y1 - 2020/10
N2 - Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25–2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06–1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04–1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09–1.31) and EHBDC (HR 1.11; 95% CI 1.01–1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
AB - Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25–2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06–1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04–1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09–1.31) and EHBDC (HR 1.11; 95% CI 1.01–1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
KW - Biliary tract cancer
KW - Gallbladder cancer
KW - Parity
KW - Reproductive factors
UR - http://www.scopus.com/inward/record.url?scp=85088102817&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088102817&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2020.04.046
DO - 10.1016/j.jhep.2020.04.046
M3 - Article
C2 - 32437829
AN - SCOPUS:85088102817
VL - 73
SP - 863
EP - 872
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 4
ER -