Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
2017
Melin, Beatrice S. | Barnholtz-Sloan, Jill S. | Wrensch, Margaret R. | Johansen, Christoffer | Il'Yasova, Dora | Kinnersley, Ben | Ostrom, Quinn T. | Labreche, Karim | Chen, Yanwen | Armstrong, Georgina | Liu, Yanhong | Eckel-Passow, Jeanette E. | Decker, Paul A. | Labussiere, Marianne | Idbaih, Ahmed | Hoang-Xuan, Khe | Di Stefano, Anna-Luisa | Mokhtari, Karima | Delattre, Jean-Yves | Broderick, Peter | Galan Hercberg, Pilar | Gousias, Konstantinos | Schramm, Johannes | Schoemaker, Minouk J. | Fleming, Sarah J. | Herms, Stefan | Heilmann, Stefanie | Noethen, Markus M. | Wichmann, Heinz-Erich | Schreiber, Stefan | Swerdlow, Anthony | Lathrop, Mark | Simon, Matthias | Sanson, Marc | Andersson, Ulrika | Rajaraman, Preetha | Chanock, Stephen | Linet, Martha | Wang, Zhaoming | Yeager, Meredith | Wiencke, John K. | Hansen, Helen | Mccoy, Lucie | Rice, Terri | Kosel, Matthew L. | Sicotte, Hugues | Amos, Christopher I. | Bernstein, Jonine L. | Davis, Faith | Lachance, Dan | Lau, Ching | Merrell, Ryan T. | Shildkraut, Joellen | Ali-Osman, Francis | Sadetzki, Siegal | Scheurer, Michael | Shete, Sanjay | Lai, Rose K. | Claus, Elizabeth B. | Olson, Sara H. | Jenkins, Robert B. | Houlston, Richard S. | Bondy, Mélissa L. | Department of Radiation Sciences [Umeå] ; Umeå University = Umeå Universitet | Case Comprehensive Cancer Center, School of Medicine ; Case Western Reserve University [Cleveland] | Department of Neurological Surgery, School of Medicine ; University of California (UC) | Institute of Human Genetics ; Universität Ulm - Ulm University [Ulm, Allemagne] | Institute of Cancer Epidemiology ; The Danish Cancer Society | Rigshospitalet [Copenhagen] ; Copenhagen University Hospital | Duke Cancer Institute Durham, North Carolina, USA. ; Duke University Medical Center | School of Public Health [Teheran] ; University of Tehran | Division of Genetics and Epidemiology ; Institute of Cancer Research (ICR) | Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) | Centre National de la Recherche Scientifique (CNRS) | Sorbonne Université (SU) | Université Pierre et Marie Curie - Paris 6 (UPMC) | Department of Medicine, Dan L. Duncan Comprehensive Cancer Center ; Baylor College of Medecine | Division of Biomedical Statistics anInformatics ; Mayo Clinic School Medicine | CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)) ; Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Department of Neurosurger ; Rheinische Friedrich-Wilhelms-Universität Bonn | Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds ; University of Leeds | Institute of Epidemiology ; Helmholtz Centre Munich | Institute of Medical Statistics and Epidemiology Munich ; Technische Universität Munchen - Technical University Munich - Université Technique de Munich (TUM) | 1st Medical Department ; University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH) ; Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel (CAU)-Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel (CAU) | Division of Breast Cancer Research London ; Institute of Cancer Research (ICR) | Department of Human Genetics Montreal ; McGill University Health Center [Montreal] (MUHC) | Genome Québec | Department of Neurosurgery ; Institut of Clinical Medicine | Division of Cancer Epidemiology and Genetics ; National Cancer Institute [Bethesda] (NCI-NIH) ; National Institutes of Health [Bethesda, MD, USA] (NIH)-National Institutes of Health [Bethesda, MD, USA] (NIH) | Department of Neurological Surgery, School of Medicine ; University of California [San Francisco] (UC San Francisco) ; University of California (UC)-University of California (UC) | Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth ; Geisel School of Medicine at Dartmouth | Department of Epidemiology and Biostatistics ; Shahrekord University | School of Public Health ; Imperial College London | Department of Neurology, Mayo Clinic Comprehensive Cancer Center ; Mayo Clinic | Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center ; Baylor College of Medecine | Department of Neurology Evanston, Illinois, USA. ; NorthShore University HealthSystem | Duke Cancer Institute Durham ; Duke University Medical Center | Cancer Control and Prevention Program, Department of Community and Family Medicine Durham ; Duke University Medical Center | Department of Surgery Durham, North ; Duke University Medical Center | Cancer and Radiation Epidemiology Unit, Gertner Institute ; Chaim Sheba Medical Center | Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine ; Tel Aviv University (TAU) | Department of Biostatistics [Oslo] ; Institute of Basic Medical Sciences [Oslo] ; Faculty of Medicine [Oslo] ; University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo] ; University of Oslo (UiO)-University of Oslo (UiO) | Keck School of Medicine [Los Angeles] ; University of Southern California (USC) | School of Public Health New Haven ; Yale University [New Haven] | Department of Neurosurgery Boston ; Brigham and Women's Hospital [Boston] | Department of Laboratory Medicine and Pathology ; University of Alberta | Division of Molecular Pathology ; Tottori University | Department of Medicine, Dan L. Duncan Comprehensive Cancer Center Baylor Houston ; Baylor College of Medecine | US National Institutes of Health (NIH) [R01CA139020, R01CA52689, P30CA125123]; McNair Medical Institute; Population Sciences Biorepository at Baylor College of Medicine; Acta Oncologica through the Royal Swedish Academy of Science; Swedish Research Council; Swedish Cancer Foundation; Cancer Research UK - Bobby Moore Fund [C1298/A8362]; Wellcome Trust; DJ Fielding Medical Research Trust; National Cancer Research Network; European Union [QLK4-CT-1999-01563]; International Union against Cancer (UICC); Mobile Manufacturers' Forum; GSM Association; UICC; Mobile Telecommunications and Health Research (MTHR) Programme; Health and Safety Executive, Department of Health and Safety Executive; UK Network Operators; Ligue Nationale Contre le Cancer; Fondation ARC; Institut National du Cancer (INCa) [PL046]; French Ministry of Higher Education and Research; program "Investissements d'avenir" [ANR-10-IAIHU-06]; Genome Quebec; le Ministere de l'Enseignement superieur, de la Recherche, de la Science et de la Technologie (MESRST) Quebec; McGill University; Deutsche Forschungsgemeinschaft [Si552, Schr285]; Deutsche Krebshilfe [70-2385-Wi2, 70-3163-Wi3, 10-6262]; BONFOR; Wellcome Trust [076113, 085475]; German Federal Ministry of Education and Research (BMBF); Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg; German National Genome Research Network (NGFN); Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) - e:Med research and funding concept [01ZX1314A]; DFG; Alfried Krupp von Bohlen und Halbach-Stiftung; BONFOR Programme of the University of Bonn, Germany; NIH [R01CA139020, R01CA52689, P50CA097257, R01CA126831, P50CA108961, P30CA15083]; Loglio Collective; National Brain Tumor Foundation; Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research; Robert Magnin Newman Endowed Chair in Neuro-oncology; National Center for Research Resources; National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI [UL1 RR024131]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01]; National Institute of Neurological Disorders and Stroke [RC1NS068222Z]; Bernie and Edith Waterman Foundation; Ting Tsung and Wei Fong Chao Family Foundation | ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010)
Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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