Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

Grants

Funding Acknowledgements

Acknowledgments GECCO: This research and all authors were funded through the NCI, NIH, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, U01 CA164930, R21 CA191312, R01201407, R01CA488857) . Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR) contract nos. HHSN268201700006I and HHSN268201200008I. This research and all authors were funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. Scientific Computing Infrastructure at Fred Hutch funded by ORIP grant S10OD028685. ASTERISK: This research and all authors were supported by a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and by the Regional Council of Pays de la Loire, the Groupement des Entreprises Fran?caises dans la Lutte contre le Cancer (GEFLUC) , the Association Anne de Bretagne Ge?ne?tique and the Ligue Re?gionale Contre le Cancer (LRCC) . We are very grateful to Dr. Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians, and students. The ATBC Study and all authors were supported by the Intramural Research Program of the U.S. NCI, NIH, Department of Health and Human Services. The CCFR ( www.coloncfr.org) and all authors were supported in part by funding from the 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 U.S. 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 article does not necessarily reflect the views or policies of the NCI, NIH or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government, any cancer registry, or the CCFR. The Colon CFR graciously thanks the generous contributions of their study participants, dedication of study staff, and the financial support from the U.S. NCI, 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) . CLUE II: This study and all authors were funded by the NCI (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 organizations imply endorsement by the U.S. government. Maryland Cancer Registry Cancer data 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 Pre-vention. 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. 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. COLO2&3: This study and all authors were funded by the NIH (R01 CA60987) . Colorectal Cancer Transdisciplinary (CORECT) Study: The CORECT Study and all authors were supported by the NCI/NIH, U.S. Department of Health and Human Services (grant nos. U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350; P01 CA196569; R01 CA201407) and National Institutes of Environmental Health Sciences, NIH (grant no. T32 ES013678) . CORSA: The 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. We kindly thank all individuals who agreed to participate in the CORSA study. Furthermore, we thank all cooperating physicians and students and the Biobank Graz of the Medical University of Graz. CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was con-ducted with Institutional Review Board approval. 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 NCI Surveillance Epidemiology and End Results program. CRCGEN: Colorectal Cancer Genetics & Genomics, Spanish study and all authors were 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) , and Junta de Castilla y Leo?n (grant LE22A10-2) . Sample collection of this work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d?Oncolog?a de Catalunya (XBTC) , Plataforma Biobancos PT13/0010/0013 and ICOBIOBANC, sponsored by the Catalan Institute of Oncology. Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE. Czech Republic CCS: This work and all authors were supported by the Grant Agency of the Czech Republic (21-27902S, 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 Charles University grants Unce/Med/006 and Progress Q28/LF1. We are thankful to all clinicians in major hospitals in the Czech Republic, without whom the study would not be practicable. We are also sincerely grateful to all patients participating in this study. DACHS: This work and all authors were 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) . We thank all participants and cooperating clinicians, and everyone who provided excellent technical assistance. DALS: This study was supported by the NIH (R01 CA48998 to M.L. Slattery) . EDRN: This work and all authors were funded and supported by the NCI, EDRN Grant (U01 CA 84968-06) . We acknowledge all contributors to the development of the resource at University of Pittsburgh School of Medicine, Department of Gastro-enterology, Department of Pathology, Hepatology and Nutrition and Biomedical Informatics. EPIC: The coordination of EPIC is financially supported by 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 and all authors are supported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Ge?ne?rale de l?Education Nationale, Institut National de la Sante?et de la Recherche Me?dicale (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 ofAndaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain) ; Swedish Cancer Society, Swedish Research Council and Regions of Ska?ne and Va?sterbotten (Sweden) ; 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) . (United Kingdom) . 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. ESTHER/VERDI. This work and all authors were supported by grants from the Baden-Wu?rttemberg Ministry of Science, Research and Arts and the German Cancer Aid. Harvard cohorts (HPFS, NHS, PHS) : HPFS and all authors are supported by the NIH (P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, and R35 CA197735) , NHS by the NIH (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, and R35 CA197735) , and PHS by the NIH (R01 CA042182) . 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. We would like to thank the participants and staff of the HPFS, NHS and PHS 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. Hawaii Adenoma Study: This study was supported by the NCI grants R01 CA072520 (to L. Le Marchand) . Kentucky: This work and all authors were supported by the following grant support: Clinical Investigator Award from Damon Runyon Cancer Research Foun-dation (CI-8) ; NCI R01CA136726. We would like to acknowledge the staff at the Kentucky Cancer Registry. LCCS: The Leeds Colorectal Cancer Study and all authors were funded by the Food Standards Agency and Cancer Research UK Programme Award (C588/A19167) . We acknowledge the contributions of Jennifer Barrett, Robin Waxman, Gillian Smith, and Emma Northwood in conducting this study. Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS and all authors were further augmented by Australian National Health and Medical Research Council grants 209057, 396414, and 1074383 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 DatabaseMEC: NIH (R37 CA054281, P01 CA033619, and R01 CA063464) . NCCCS I & II: We acknowledge funding support for this project and to all authors from the NIH, R01 CA66635 and P30 DK034987. We would like to thank the study participants, and the NC Colorectal Cancer Study staff. NFCCR: This work was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821) ; the NIH, U.S. Department of Health and Human Services (U01 CA74783) ; and NCI of Canada grants (18223 and 18226) . The authors wish to acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Ge?nome Que?bec Innovation Centre, Montre?al, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to M.O. Woods by the Canadian Cancer Society Research Institute. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Funding was provided to the study and allauthors by NIH, Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. The authors thank the PLCO Cancer Screening Trial screening center 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 NCI, SEER program. The results reported here and the conclusions derived are the sole responsibility of the authors. SEARCH: The University of Cambridge has received salary support in respect of PDPP from the NHS in the East of England through the Clinical Academic Reserve. Cancer Research UK (C490/A16561) ; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge. We thank the SEARCH team. SELECT: Research reported in this publication was supported in part by the NCI of the NIH under award numbers U10 CA37429 (to C.D. Blanke) , and UM1 CA182883 (to C.M. Tangen and I.M. Thompson) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank the research and clinical staff at the sites that participated on 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. SMS and REACH: This work was supported by the NCI (grant P01 CA074184, to J.D. Potter and P.A. Newcomb, grants R01 CA097325, R03 CA153323, and K05 CA152715, to P.A. Newcomb, and the National Center for Advancing Transla-tional Sciences at the National Institutes of Health (grant KL2 TR000421, to A.N. Burnett-Hartman) . Swedish Mammography Cohort and Cohort of Swedish Men: This work is 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: This research has been conducted using the UK Biobank Resource under application number 8614. VITAL: This study was funded by the NIH (K05 CA154337, to E. White) . WHI: The WHI program and all authors are funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http:// www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf.