TY - JOUR
T1 - Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes and tumor location
AU - Labadie, Julia D.
AU - Harrison, Tabitha A.
AU - Banbury, Barbara
AU - Amtay, Efrat L.
AU - Bernd, Sonja
AU - Brenner, Hermann
AU - Buchanan, Daniel D.
AU - Campbell, Peter T.
AU - Cao, Yin
AU - Chan, Andrew T.
AU - Chang-Claude, Jenny
AU - Englishc, Dallas
AU - Figueiredo, Jane C.
AU - Gallingerc, Steven J.
AU - Gilesc, Graham G.
AU - Gunter, Marc J.
AU - Hoffmeisterc, Michael
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Lin, Yi
AU - Milnec, Roger L.
AU - Moreno, Victor
AU - Murphyc, Neil
AU - Ogino, Shuji
AU - Phipps, Amanda I.
AU - Sakoda, Lori C.
AU - Slattery, Martha L.
AU - Southey, Melissa C.
AU - Sun, Wei
AU - Thibodeau, Stephen N.
AU - Van Guelpen, Bethany
AU - Zaidi, Syed H.
AU - Peters, Ulrike
AU - Newcomb, Polly A.
N1 - Funding Information:
DACHS: This work was supported by the German Research Council (BR 1704/6–1, BR 1704/6–3, BR 1704/6–4, CH 117/1–1, HO 5117/2–1, HE 5998/2–1, KL 2354/3–1, RO 2270/8–1, and BR 1704/17–1), the Interdisciplinary Research Program of the National Center for Tumor Diseases, Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A, and 01ER1505B). DALS: National Institutes of Health (R01 CA48998).
Funding Information:
EPIC: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Va€sterbotten (Sweden).
Funding Information:
TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. MCCS: Melbourne Collaborative Cohort Study cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. NSHDS: The NSHDS investigators thank the Biobank Research Unit at Umeå University, the Va€sterbotten Intervention Programme, the Northern Sweden MONICA study, and Region Va€sterbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017–00650).
Funding Information:
Genetics and Epidemiology of Colorectal Cancer Consortium: This work was supported by the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services R01 CA176272, U01 CA137088, and U01 CA164930. This research was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA015704.
Funding Information:
NSHDS: Swedish Cancer Society; Cancer Research Foundation in Northern Sweden; Swedish Research Council; J C Kempe Memorial Fund; Faculty of Medicine, Umeå University, Umeå, Sweden; and Cutting-Edge Research Grant from the County Council of Va€sterbotten, Sweden.
Funding Information:
Acknowledgments: SCCFR: The authors would like to thank the study participants and staff of the Hormones and Colon Cancer and Seattle Cancer Family Registry studies (CORE studies). CPS-II: The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. DACHS: We thank all participants and cooperating clinicians, and Ute Handte-Daub, Utz Benscheid, Muhabbet Celik, and Ursula Eilber for excellent technical assistance. EPIC: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. Harvard cohort (NHS): The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. We 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,
Funding Information:
Fred Hutchinson Cancer Research Center investigators were also supported by National Institutes of Health T32 CA094880 and National Institutes of Health K05 CA152715.
Funding Information:
Harvard cohort (NHS): NHS is supported by the National Institutes of Health (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, R35 CA197735, K07 CA190673, and P50 CA127003).
Funding Information:
The Colon Cancer Family Registry (CCFR) was supported in part by National Cancer Institute/National Institutes of Health award number U01 CA167551 and through National Cancer Institute/National Institutes of Health U01/U24 cooperative agreements with the following CCFR sites: Ontario (OFCCR) (CA074783), Seattle (SCCFR) (CA074794 and R01 CA076366), and Australasian (ACCFR) (CA074778 and CA097735). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government, any cancer registry, or the CCFR.
Funding Information:
MCCS: This cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian National Health and Medical Research Council grants 509348, 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases, and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database.
Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: Adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2- sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
AB - Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: Adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2- sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
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U2 - 10.1093/JNCICS/PKAA042
DO - 10.1093/JNCICS/PKAA042
M3 - Article
AN - SCOPUS:85100740939
SN - 2515-5091
VL - 4
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 5
M1 - pkaa042
ER -
