Document is current

Article History

Received: 25 October 2022

Accepted: 13 March 2023

First Online: 12 May 2023

Acknowledgements

: The authors would like to thank the participants of the individual studies contributing to the BCAC and the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for their participation in these studies, along with the principal investigators of these consortia for generating the data used for this analysis and for making these data available in the public domain. Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)-specific acknowledgements include French Association STudy Evaluating RISK for Sporadic Colorectal Cancer (ASTERISK); we are very grateful to B. Buecher without whom this project would not have existed. We also thank all participants in this study, as well as all the physicians, technicians and students. The CCFR graciously thanks the generous contributions of their study participants and acknowledge the dedication of study staff and the financial support from the US National Cancer Institute, without which this important registry would not exist. The authors would like to thank the study participants and staff of the Seattle CCFR and the Hormones and Colon Cancer study (CORE Studies). We thank the participants of Clue II and appreciate the continued efforts of the staff at the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the Clue II Cohort Study. The authors would like to thank the COLON and NQplus investigators at Wageningen University & Research and the involved clinicians in the participating hospitals. We kindly thank all individuals who agreed to participate in the Colorectal Cancer Study of Austria (CORSA) study. Furthermore, we thank all cooperating physicians and students and the Biobank Graz of the Medical University of Graz. 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 programme. For the Czech Republic Colorectal Cancer Study (CCS), we are thankful to all clinicians in major hospitals in the Czech Republic, without whom the study would not have been practicable. We are also sincerely grateful to all participants in this study. We thank all participants and cooperating clinicians in Darmkrebs: Chancen der Verhütung durch Screening (DACHS), and everyone who provided excellent technical assistance. We acknowledge all contributors to the development of the Early Detection Research Network (EDRN) resource at University of Pittsburgh School of Medicine, Department of Gastroenterology, Department of Pathology, Hepatology and Nutrition and Biomedical Informatics. For European Prospective Investigation into Cancer and Nutrition (EPIC), where authors are identified as personnel of the International Agency for Research on Cancer/WHO, 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/WHO. We are sincerely grateful to all participants who were recruited as part of the EPICOLON project. We acknowledge the Spanish National DNA Bank, Biobank of Hospital Clínic–IDIBAPS and Biobanco Vasco for the availability of the samples. The work was carried out (in part) at the Esther Koplowitz Centre, Barcelona. For the Harvard cohorts (HPFS, NHS, PHS), 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 acknowledge Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital as home of the NHS. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities and cancer centres. Participating central cancer registries include Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia and Wyoming. The authors assume full responsibility for analyses and interpretation of data from these registries. We would also like to acknowledge the staff at the Kentucky Cancer Registry. We acknowledge the contributions of Jennifer Barrett, Robin Waxman, Gillian Smith and Emma Northwood in conducting the Leeds Colorectal Cancer Study (LCCS) study. We would like to thank North Carolina Case-Control Study (NCCCS) I and NCCCS II study participants, and the NC Colorectal Cancer Study staff. Northern Swedish Health and Disease Study (NSHDS) investigators thank the Västerbotten Intervention Programme, the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, the Biobank Research Unit at Umeå University and Biobanken Norr at Region Västerbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council. The authors thank the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial screening centre investigators and the staff from Information Management Services Inc and Westat Inc. Most importantly, we thank the study participants for their contributions that made this study possible. Cancer incidence data have been provided by the District of Columbia Cancer Registry, Georgia Cancer Registry, Hawaii Cancer Registry, Minnesota Cancer Surveillance System, Missouri Cancer Registry, Nevada Central Cancer Registry, Pennsylvania Cancer Registry, Texas Cancer Registry, Virginia Cancer Registry and Wisconsin Cancer Reporting System. All are supported in part by funds from the Center for Disease Control and Prevention, National Program for Central Registries, local states, or by the National Cancer Institute, Surveillance, Epidemiology and End Results programme. The results reported here and the conclusions derived are the sole responsibility of the authors. We thank the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) team. We thank the research and clinical staff at the sites that participated in the Selenium and Vitamin E Prevention Trial (SELECT) study, without whom the trial would not have been successful. We are also grateful to the 35,533 dedicated men who participated in SELECT. The authors thank the Women’s Health Initiative (WHI) investigators and staff for their dedication, and the study participants for making the programme possible. A full listing of WHI investigators can be found at:

: Summary genetic association data for select cancer endpoints were obtained from the public domain: breast cancer (); and overall prostate cancer (). Summary genetic association data for colorectal cancer can be accessed by contacting GECCO (kafdem at fredhutch.org). Summary genetic association data on advanced prostate cancer can be accessed by contacting PRACTICAL (practical at icr.ac.uk). Summary genetic association data on type 2 diabetes from Vujkovic et al [] (can be accessed through dbGAP under accession number phs001672.v3.p1 (pha004945.1 refers to the European-specific summary statistics). UK Biobank data can be accessed by registering with UK Biobank and completing the registration form in the Access Management System (AMS) ().

: JY is supported by a Cancer Research UK Population Research Postdoctoral Fellowship (C68933/A28534). JY, EEV, SJL, RMM and KKT are supported by Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) (). AC acknowledges funding from a Medical Research Council PhD studentship (MR/N013794/1). EEV is supported by a Diabetes UK RD Lawrence Fellowship (17/0005587). EEV and CJB are supported by Diabetes UK (17/0005587) and the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (IIG_2019_2009). MV is supported by I01-BX003362 from VA Office of R&D. RMM is a National Institute for Health Research Senior Investigator (NIHR202411). RMM is also supported by the NIHR Bristol Biomedical Research Centre, which is funded by the NIHR (BRC-1215-20011) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. Department of Health and Social Care disclaimer: the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Disclaimer: where authors are identified as personnel of the International Agency for Research on Cancer/WHO, 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/WHO. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration and was supported by award no. MVP000. This publication does not represent the views of the Department of Veterans Affairs, the US Food and Drug Administration, or the US government. This research was also supported by funding from the Department of Veterans Affairs awards I01- BX003362 (K-MC). The study sponsor/funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Funding specific to GECCO was from National Cancer Institute, NIH, US Department of Health and Human Services (U01 CA137088, R01 CA059045, U01 CA164930, R21 CA191312, R01201407). Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR) contract number HHSN268201700006I and HHSN268201200008I . This research was funded in part through the NIH/National Cancer Institute (NCI) Cancer Center Support grant P30 CA015704. Scientific Computing Infrastructure at Fred Hutch was funded by ORIP grant S10OD028685. ASTERISK is a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and is supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC). The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study is supported by the Intramural Research Program of the US National Cancer Institute, NIH, Department of Health and Human Services. CLUE II funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network; P30 CA006973), National Institute on Aging (U01 AG18033) and the American Institute for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organisations imply endorsement by the US government. Cancer data from Maryland were provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund. The collection and availability of cancer registry data are also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services. The work of ColoCare was supported by the NIH (grant numbers R01 [C.I. Li/C. M. Ulrich], U01 CA206110 [C. M. Ulrich/C. I. Li/E. M. Siegel/J. C. Figueiredo/G. A. Colditz], 2P30CA015704- 40 [G. Gilliland], R01 CA207371 [C. M. Ulrich/C. I. Li]), the Matthias Lackas-Foundation, the German Consortium for Translational Cancer Research, and the EU TRANSCAN initiative. The CCFR () is supported in part by funding from the National Cancer Institute (NCI), NIH (award U01 CA167551). Support for case ascertainment was provided in part from the Surveillance, Epidemiology, and End Results (SEER) Program and the following US state cancer registries: AZ, CO, MN, NC, NH; and by the Victoria Cancer Registry (Australia) and Ontario Cancer Registry (Canada). The CCFR Set-1 (Illumina 1M/1M-Duo) and Set-2 (Illumina Omni1-Quad) scans were supported by NIH awards U01 CA122839 and R01 CA143247 (to G. Casey. The CCFR Set-3 (Affymetrix Axiom CORECT Set array) was supported by NIH award U19 CA148107 and R01 CA81488 (to S. B. Gruber). The CCFR Set-4 (Illumina OncoArray 600K SNP array) was supported by NIH award U19 CA148107 (to S. B. Gruber) and by the Center for Inherited Disease Research (CIDR), which is funded by the NIH to the Johns Hopkins University, contract number HHSN268201200008I. Additional funding for the OFCCR/ARCTIC was through award GL201-043 from the Ontario Research Fund (to B. W. Zanke), award 112746 from the Canadian Institutes of Health Research (to T. J. Hudson), through a Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society (to S. Gallinger), and through generous support from the Ontario Ministry of Research and Innovation. The SFCCR Illumina HumanCytoSNP array was supported in part through NCI/NIH awards U01/U24 CA074794 and R01 CA076366 (to P. A. Newcomb). The content of this manuscript does not necessarily reflect the views or policies of the NCI, NIH or any of the collaborating centres in the CCFR, nor does mention of trade names, commercial products or organisations imply endorsement by the US government, any cancer registry or the CCFR. The COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life (COLON) study is sponsored by Wereld Kanker Onderzoek Fonds, including funds from grant 2014/1179 as part of the World Cancer Research Fund International Regular Grant Programme, by Alpe d’Huzes and the Dutch Cancer Society (UM 2012–5653, UW 2013-5927, UW2015-7946), and by TRANSCAN (JTC2012-MetaboCCC, JTC2013-FOCUS). The NQplus study is sponsored as follows: by a ZonMW investment grant (98-10030); by the project PREVention of diabetes through lifestyle intervention and population studies in Europe and around the World (PREVIEW) project, which received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant no. 312057; by funds from TI Food and Nutrition (cardiovascular health theme), a public–private partnership on precompetitive research in food and nutrition; and by the Food Biomarker Alliance (FOODBALL), a project from JPI Healthy Diet for a Healthy Life. The CORECT Study was supported by the National Cancer Institute, NIH (NCI/NIH), US Department of Health and Human Services (grant numbers U19 CA148107, R01 CA081488, P30 CA014089, R01 CA197350; P01 CA196569; R01 CA201407; R01 CA242218), National Institutes of Environmental Health Sciences, NIH (grant number T32 ES013678) and a generous gift from Daniel and Maryann Fong. The Colorectal Cancer Study of Austria (CORSA) study was funded by Austrian Research Funding Agency (FFG) BRIDGE (grant 829675, to A. Gsur), the ‘Herzfelder’sche Familienstiftung’ (grant to A. Gsur) and was supported by COST Action BM1206. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was conducted with institutional review board approval. Colorectal Cancer Genetics & Genomics, Spanish study (CRCGEN) was supported by Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– (grants PI14-613 and PI09-1286), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (grant 2017SGR723), Junta de Castilla y León (grant LE22A10-2), the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE and the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), action Genrisk. Sample collection of this work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC), Plataforma Biobancos PT13/0010/0013 and ICOBIOBANC, sponsored by the Catalan Institute of Oncology. We thank CERCA Programme, Generalitat de Catalunya for institutional support. The work of the Czech Republic CCS was supported by the Grant Agency of the Czech Republic (18-09709S, 20-03997S), by the Grant Agency of the Ministry of Health of the Czech Republic (grants AZV NV18/03/00199 and AZV NV19-09-00237) and by Charles University grants Unce/Med/006 and Progress Q28/LF1. The work of Darmkrebs: Chancen der Verhutung durch Screening (DACHS) 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 (NCT), Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A and 01ER1505B). The Diet, Activity, and Lifestyle Study (DALS) was supported by NIH (R01 CA48998 to M. L. Slattery). The work of the Early Detection Research Network (EDRN) is funded and supported by the NCI, EDRN Grant (U01 CA 84968-06). The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by the following bodies: Danish Cancer Society (Denmark); 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 Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (UK). The work of EPICOLON was supported by grants from Fondo de Investigación Sanitaria/FEDER (PI08/0024, PI08/1276, PS09/02368, P111/00219, PI11/00681, PI14/00173, PI14/00230, PI17/00509, 17/00878, PI20/00113, PI20/00226, Acción Transversal de Cáncer), Xunta de Galicia (PGIDIT07PXIB9101209PR), Ministerio de Economia y Competitividad (SAF07-64873, SAF 2010-19273, SAF2014-54453R), Fundación Científica de la Asociación Española contra el Cáncer (GCB13131592CAST), Beca Grupo de Trabajo ‘Oncología’ AEG (Asociación Española de Gastroenterología), Fundación Privada Olga Torres, FP7 CHIBCHA Consortium, Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya, 2014SGR135, 2014SGR255, 2017SGR21, 2017SGR653), Catalan Tumour Bank Network (Pla Director d’Oncologia, Generalitat de Catalunya), PERIS (SLT002/16/00398, Generalitat de Catalunya), CERCA Programme (Generalitat de Catalunya) and COST Action BM1206 and CA17118; CIBERehd is funded by the Instituto de Salud Carlos III.The work of Epidemiological investigations of the chances of preventing, recognizing early and optimally treating chronic diseases in an elderly population (ESTHER)/VERDI was supported by grants from the Baden-Württemberg Ministry of Science, Research and Arts and the German Cancer Aid. In the Harvard cohorts, Health Professionals Follow-Up Study (HPFS) is supported by the NIH (P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, and R35 CA197735), Nurses’ Health Study (NHS) by the NIH (P01 CA087969, UM1 CA186107, R01 CA137178, R01 CA151993, and R35 CA197735), and Physicians’ Health Study (PHS) by the NIH (R01 CA042182). The Hawaii Adenoma Study is supported by NCI grant R01 CA72520. The Hwasun Cancer Epidemiology Study–Colon and Rectum Cancer (HCES-CRC) is supported by grants from Chonnam National University Hwasun Hospital, HCRI15011-1. In Kentucky, work was supported by a Clinical Investigator Award from Damon Runyon Cancer Research Foundation (CI-8) and grant NCI R01CA136726. The Leeds Colorectal Cancer Study (LCCS) was funded by the Food Standards Agency and Cancer Research UK Programme Award (C588/A19167). Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC 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 (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. Multiethnic Cohort (MEC) was supported by NIH grants (R37 CA54281, P01 CA033619 and R01 CA063464). The work of Molecular Epidemiology of Colorectal Cancer (MECC) was supported by the NIH, US Department of Health and Human Services (R01 CA081488, R01 CA197350, U19 CA148107, R01 CA242218) and a generous gift from Daniel and Maryann Fong. The work of Memorial Sloan Kettering Cancer Center (MSKCC) at Sloan Kettering in New York was supported by the Robert and Kate Niehaus Center for Inherited Cancer Genomics and the Romeo Milio Foundation. Moffitt was supported by funding from the NIH (grant numbers R01 CA189184, P30 CA076292), Florida Department of Health Bankhead-Coley Grant 09BN-13, and the University of South Florida Oehler Foundation. Moffitt contributions were supported in part by the Total Cancer Care Initiative, Collaborative Data Services Core and Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center (grant number P30 CA076292). We acknowledge funding support for NCCCS I & II from the NIH, R01 CA66635 and P30 DK034987. This work of Newfoundland Colorectal Cancer Registry (NFCCR) was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821), the NIH, US Department of Health and Human Services (U01 CA74783), and National Cancer Institute of Canada grants (18223 and 18226). The authors wish to acknowledge the contribution of A. Belisle and the genotyping team of the McGill University and Génome Québec Innovation Centre, Montréal, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to M. O. Woods by the Canadian Cancer Society Research Institute. The Northern Swedish Health and Disease Study (NSHDS) research was supported by Biobank Sweden through funding from the Swedish Research Council (VR 2017-00650, VR 2017-01737), the Swedish Cancer Society (CAN 2017/581), Region Västerbotten (VLL-841671, VLL-833291), Knut and Alice Wallenberg Foundation (VLL-765961), and the Lion’s Cancer Research Foundation (several grants) and Insamlingsstiftelsen, both at Umeå University. Ohio State University Medical Center (OSUMC) Ohio Colorectal Cancer Prevention Initiative (OCCPI) funding was provided by Pelotonia and HNPCC funding was provided by the NCI (CA16058 and CA67941). The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics were supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Funding was provided by NIH, Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446 and NIH GEI U01 HG 004438. For SEARCH, the University of Cambridge has received salary support in respect of PDDP from the NHS in the East of England through the Clinical Academic Reserve. Cancer Research UK (C490/A16561) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge also provided support. SELECT research reported in this publication was supported in part by the National Cancer Institute of the NIH under Award Numbers U10 CA37429 (C. D. Blanke) and UM1 CA182883 (C. M. Tangen/I. M. Thompson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The work of Screening Markers For Colorectal Disease Study and Colonoscopy and Health Study (SMS-REACH) was supported by the National Cancer Institute (grant P01 CA074184 [to J. D. Potter and P. A. Newcomb], grants R01 CA097325, R03 CA153323 and K05 CA152715 [to PAN]) and the National Center for Advancing Translational Sciences at the NIH (grant KL2 TR000421 [to ANB-H]). The Swedish Low-risk Colorectal Cancer Study was supported by grants from the Swedish Research Council (K2015-55X-22674-01-4, K2008-55X-20157-03-3, K2006-72X-20157-01-2) and the Stockholm County Council (ALF project). The Swedish Mammography Cohort and Cohort of Swedish Menwas supported by the Swedish Research Council /Infrastructure grant, the Swedish Cancer Foundation, and the Karolinska Institute´s Distinguished Professor Award to A. Wolk. UK Biobank research has been conducted using the UK Biobank Resource under Application Number 8614. VITamin D and OmegA-3 TriaL (VITAL) was supported by NIH (K05 CA154337). The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung and Blood Institute, NIH, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C.

: DG is employed part-time by Novo Nordisk for work unrelated to that presented here. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: JY, EB, DG and KKT contributed to study conception and design, acquisition of data, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content, and gave final approval of the version to be published. AC contributed to analysis of data, drafting the article and revising it critically for important intellectual content, and gave final approval of the version to be published. MV contributed to acquisition of data, drafting the article and revising it critically for important intellectual content, and gave final approval of the version to be published. CJB, EEV, KB, RMM, OD, SJL, VM, KC, BFV, PST, MJG, JH, AJP, PDPP, RES, SG, MAJ and RKP contributed to study design, drafting the article and revising it critically for important intellectual content, and gave final approval of the version to be published. JY is the guarantor of this work.