Journal article

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Yingchang Lu, Alicia Beeghly-Fadiel, Lang Wu, Xingyi Guo, Bingshan Li, Joellen M Schildkraut, Hae Kyung Im, Yian A Chen, Jennifer B Permuth, Brett M Reid, Jamie K Teer, Kirsten B Moysich, Irene L Andrulis, Hoda Anton-Culver, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Javier Benitez, Line Bjorge Show all

Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2018

Grants

Awarded by US National Cancer Institute GAME-ONPost-GWAS Initiative


Awarded by Wellcome Trust


Awarded by NIH


Awarded by Canadian Institutes of Health Research


Awarded by European Commission


Awarded by Canadian Institutes for Health Research


Awarded by U.S. Army Medical Research and Materiel Command


Awarded by National Health & Medical Research Council of Australia


Awarded by National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS)


Awarded by Innovative Research Team in University (PCSIRT) in China


Awarded by Instituto de Salud Carlos III


Awarded by Ministerio de Economia y Competitividad


Awarded by Department of Defense


Awarded by National Institutes of Health


Awarded by Ovarian Cancer Research Fund and National Institutes of Health


Awarded by Dutch Cancer Society


Awarded by Health Research Fund (FIS)


Awarded by ISCIII RETIC (Spain)


Awarded by Cancer Research UK


Awarded by Medical Research Council


Awarded by German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research


Awarded by Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research Technology


Awarded by Roswell Park Cancer Institute Alliance Foundation


Awarded by NCI


Awarded by National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea


Awarded by American Cancer Society Early Detection Professorship


Awarded by National Center for Advancing Translational Sciences (NCATS)


Awarded by Swedish Cancer Society


Awarded by National Cancer Institute, Bethesda, MD


Awarded by Danish Cancer Society, Copenhagen, Denmark


Awarded by Malaysian Ministry of Higher Education


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by DOD Ovarian Cancer Research Program


Awarded by National Cancer Institute


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by NIH/NCI


Awarded by National Institute of Health


Awarded by NIH, National Institute of Environmental Health Sciences


Awarded by Health Canada


Awarded by Imperial Experimental Cancer Research Centre


Awarded by NIH (NCI)


Awarded by American Cancer Society


Awarded by Lon V Smith Foundation


Awarded by UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge


Awarded by California Cancer Research Program


Awarded by National Health and Medical Research Council of Australia


Awarded by Cancer Institute NSW


Awarded by National Science Centren


Awarded by Vanderbilt University Medical Center's BioVU


Awarded by Vanderbilt CTSA from NCATS/NIH


Awarded by Gynecologic Cancer Center of Excellence


Awarded by Australian NHMRC


Awarded by Intramural Research Program of the NIH, National Institute of Environmental Health Sciences


Awarded by National Health Research and Development Program, Health Canada


Awarded by National Institutes of Health, National Cancer Institute


Awarded by National Health and Medical Research Council Enabling Grants



Funding Acknowledgements

The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI. 07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ONPost-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the NIH [U19-CA148112 (to T. A. Sellers), R01-CA149429 (to C. M. Phelan), and R01-CA058598 (to M. T. Goodman); Canadian Institutes of Health Research (MOP-86727 (to L. E. Kelemen)] and the Ovarian Cancer Research Fund (to A. Berchuck). The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). Funding for individual studies: AAS: NIH (RO1-CA142081); AOV: The Canadian Institutes for Health Research (MOP-86727); AUS: The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BAV: ELAN Funds of the University of Erlangen-Nuremberg; BEL: National Kankerplan; BGS: Breast Cancer Now, Institute of Cancer Research; BVU: Vanderbilt CTSA grant from the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) (ULTR000445); CAM: National Institutes of Health Research Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Cancer Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CNI: Instituto de Salud Carlos III (PI 12/01319); Ministerio de Economia y Competitividad (SAF2012); COE: Department of Defense (W81XWH-11-2-0131); CON: National Institutes of Health (R01-CA063678, R01-CA074850; R01CA080742); DKE: Ovarian Cancer Research Fund and National Institutes of Health 1R01CA211574 (J. M. Schildkraut); DOV: National Institutes of Health R01-CA112523 and R01-CA87538; EMC: Dutch Cancer Society (EMC 20146699); EPC: 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, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy 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); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom); GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and the German Cancer Research Center (DKFZ); GRC: This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund; GRR: Roswell Park Cancer Institute Alliance Foundation, P30 CA016056; HAW: U.S. National Institutes of Health (R01CA58598, N01-CN-55424 and N01-PC-67001); HJO: Intramural funding; Rudolf-Bartling Foundation; HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki University Research Fund; HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981 MO1-RR000056 R01-CA126841); HUO: Intramural funding; Rudolf-Bartling Foundation; JGO: JSPS KAKENHI grant; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; LUN: ERC-2011-AdG 294576-risk factors cancer, Swedish Cancer Society, Swedish Research Council, Beta Kamprad Foundation; MAC: NIH (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; MAL: Funding for this study was provided by research grant R01 CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAS: Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; MCC: Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) grants number 209057, 251533, 396414, and 504715; MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); MEC: NIH (CA54281, CA164973, CA63464); MOF: Moffitt Cancer Center, Merck Pharmaceuticals, the state of Florida, Hillsborough County, and the city of Tampa; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of Health R01-CA54419 and P50-CA105009 and Department of Defense W81XWH-10-1-02802; NHS: UM1 CA186107, P01 CA87969, R01 CA49449, R01-CA67262, UM1 CA176726; NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720, and P30-CA008748) and the Cancer Institute of New Jersey; NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; NTH: Radboud University Medical Centre; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142) and Brisbane Women's Club; ORE: OHSU Foundation; OVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; PLC: Intramural Research Program of the National Cancer Institute; POC: Pomeranian Medical University; POL: Intramural Research Program of the National Cancer Institute; PVD: Canadian Cancer Society and Cancer Research Society GRePEC Program; RBH: National Health and Medical Research Council of Australia; RMH: Cancer Research UK, Royal Marsden Hospital; RPC: National Institute of Health (P50 CA159981, R01CA126841); SEA: Cancer Research UK (C490/A10119 C490/ A10124); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; SIS: NIH, National Institute of Environmental Health Sciences, Z01 ES044005 and Z01-ES049033; SMC: The Swedish Research Council; SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); STA: NIH grants U01 CA71966 and U01 CA69417; SWE: Swedish Cancer foundation, WeCanCureCancer and arKampMotCancer foundation; SWH: NIH (NCI) grant R37-CA070867; TBO: National Institutes of Health (R01-CA106414-A2), American Cancer Society (CRTG-00-196-01-CCE), Department of Defense (DAMD17-98-1-8659), Celma Mastery Ovarian Cancer Foundation; TOR: NIH grants R01 CA063678 and R01 CA063682; UCI: NIH R01-CA058860 and the Lon V Smith Foundation grant LVS-39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; UKR: Cancer Research UK (C490/A6187), UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; USC: P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and California Cancer Research Program (00-01389V-20170, 2II0200); VAN: BC Cancer Foundation, VGH & UBC Hospital Foundation; VTL: NIH K05CA154337; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 & ID 628903.Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16; WOC: National Science Centren (N N301 5645 40). The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of the Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. The OncoArray and COGS genotyping projects would not have been possible without the contributions of the following: Per Hall (COGS); Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang (BCAC), Marjorie J. Riggan (OCAC), Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Jonathan P. Tyrer, Siddhartha Kar, Alison M. Dunning, Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, Anna Gonzalez-Neira and the staff of the CNIO genotyping unit, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissiere and Frederic Robidoux and the staff of the McGill University and Genome Quebec Innovation Centre, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. We pay special tribute to the contribution of Professor Brian Henderson to the GAME-ON consortium and to Olga M. Sinilnikova for her contribution to CIMBA and for her part in the initiation and coordination of GEMO until she sadly passed away on the 30th June 2014. We thank the study participants, doctors, nurses, clinical and scientific collaborators, health care providers and health information sources who have contributed to the many studies contributing to this manuscript.Acknowledgements for individual studies: AOV: We thank Jennifer Koziak, Mie Konno, Michelle Darago, Faye Chambers and the Tom Baker Cancer Centre Translational Laboratories; AUS: The AOCS also acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found at www.aocstudy.org. We would like to thank all of the women who participated in these research programs; BEL: We would like to thank Gilian Peuteman, Thomas Van Brussel, Annick Van den Broeck and Joke De Roover for technical assistance; BGS: The BGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. We thank the Study staff, study participants, doctors, nurses, health care providers and health information sources who have contributed to the study; BVU: The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center's BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH; CAM: This work was supported by Cancer Research UK; the University of Cambridge; National Institute for Health Research Cambridge Biomedical Research Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CHN: To thank all members of Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital and Department of Molecular Biology, Hebei Medical University, Fourth Hospital; COE: Gynecologic Cancer Center of Excellence (W81XWH-11-2-0131); CON: The cooperation of the 32 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data; DKE: OCRF; EPC: To thank all members and investigators of the Rotterdam Ovarian Cancer Study. Dutch Cancer Society (EMC 2014-6699); GER: The German Ovarian Cancer Study (GER) thank Ursula Eilber for competent technical assistance; HOC: The study was supported by the Helsinki University Research Fund; JGO: JSPS KAKENHI grant; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LUN: ERC-2011-AdG, Swedish Cancer Society, Swedish Research Council; MAS: We would like to thank Famida Zulkifli and Ms Moey for assistance in patient recruitment, data collection and sample preparation. The Malaysian Ovarian Cancer Genetic Study is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HIR/MOHE/06) and charitable funding from Cancer Research Initiatives Foundation; MCC: MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 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; MOF: the Total Cancer Care Protocol and the Collaborative Data Services and Tissue Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute, an NCI designated Comprehensive Cancer Center (P30-CA076292), Merck Pharmaceuticals and the state of Florida; NHS: The NHS/NHSII studies thank 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, and WY; NJO: L. Paddock, M. King, U. Chandran, A. Samoila, and Y. Bensman; OPL: Members of the OPAL Study Group (http://opalstudy.qimrberghofer.edu.au/); RPC: National Institute of Health (P50 CA159981, R01CA126841); SEA: SEARCH team, Craig Luccarini, Caroline Baynes, Don Conroy; SIS: The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033); SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: To thank all members of Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators; SWE: Swedish Cancer Foundation, WeCanCureCancer and arKampMotCancer Foundation; SWH: The SWHS is supported primarily by NIH grant R37-CA070867. We thank the participants and the research staff of the Shanghai Women's Health Study for making this study possible; UCI: The UCI Ovarian Cancer Study is supported by the National Institutes of Health, National Cancer Institute grants CA58860, and the Lon V Smith Foundation grant LVS-39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: We particularly thank I. Jacobs, M. Widschwendter, E. Wozniak, A. Ryan, J. Ford and N. Balogun for their contribution to the study; UKR: Carole Pye; VAN: BC Cancer Foundation, VGH & UBC Hospital Foundation; WMH: We thank the Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, which is funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16.