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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

About this Publication
Title
Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
Pubmed ID
28346443 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat. Genet. 2017 May; Volume 49 (Issue 5): Pages 789-794
Authors
Melin BS, Barnholtz-Sloan JS, Wrensch MR, Johansen C, Il'yasova D, Kinnersley B, Ostrom QT, Labreche K, Chen Y, Armstrong G, Liu Y, Eckel-Passow JE, Decker PA, Labussière M, Idbaih A, Hoang-Xuan K, Di Stefano AL, Mokhtari K, Delattre JY, Broderick P, ...show more Galan P, Gousias K, Schramm J, Schoemaker MJ, Fleming SJ, Herms S, Heilmann S, Nöthen MM, Wichmann HE, Schreiber S, Swerdlow A, Lathrop M, Simon M, Sanson M, Andersson U, Rajaraman P, Chanock S, Linet M, Wang Z, Yeager M, GliomaScan Consortium, Wiencke JK, Hansen H, McCoy L, Rice T, Kosel ML, Sicotte H, Amos CI, Bernstein JL, Davis F, Lachance D, Lau C, Merrell RT, Shildkraut J, Ali-Osman F, Sadetzki S, Scheurer M, Shete S, Lai RK, Claus EB, Olson SH, Jenkins RB, Houlston RS, Bondy ML
Affiliations
  • Department of Radiation Sciences, Umeå University, Umeå, Sweden.
  • Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
  • Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark and Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, USA.
  • Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
  • Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.
  • Université Paris 13 Sorbonne Paris Cité, INSERM U557, INRA U1125, CNAM, Paris, France.
...show more
  • Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
  • Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
  • Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Helmholtz Center Munich, Institute of Epidemiology I, Munich, Germany.
  • 1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Génome Québec, Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
  • Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
  • Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA.
  • Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.
  • Department of Biostatistics, University of Texas Maryland Anderson Cancer Center, Houston, Texas, USA.
  • Departments of Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • School of Public Health, Yale University, New Haven, Connecticut, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
Abstract

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 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 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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