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Nat Genet. 2017 May;49(5):789-794. doi: 10.1038/ng.3823. Epub 2017 Mar 27.

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

Author information

1
Department of Radiation Sciences, Umeå University, Umeå, Sweden.
2
Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
3
Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
4
Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA.
5
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark and Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
6
Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, USA.
7
Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
8
Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA.
9
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
10
Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.
11
Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
12
Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
13
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
14
Université Paris 13 Sorbonne Paris Cité, INSERM U557, INRA U1125, CNAM, Paris, France.
15
Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
16
Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
17
Institute of Human Genetics, University of Bonn, Bonn, Germany.
18
Helmholtz Center Munich, Institute of Epidemiology I, Munich, Germany.
19
Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.
20
Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany.
21
1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
22
Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
23
Génome Québec, Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
24
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
25
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
26
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
27
School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
28
Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
29
Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
30
Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA.
31
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
32
Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.
33
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
34
Department of Biostatistics, University of Texas Maryland Anderson Cancer Center, Houston, Texas, USA.
35
Departments of Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
36
School of Public Health, Yale University, New Haven, Connecticut, USA.
37
Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
38
Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
39
Division of Molecular Pathology, Institute of Cancer Research, London, UK.

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.

PMID:
28346443
PMCID:
PMC5558246
DOI:
10.1038/ng.3823
[Indexed for MEDLINE]
Free PMC Article

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