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Sci Rep. 2018 May 9;8(1):7352. doi: 10.1038/s41598-018-24580-z.

Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21.

Author information

1
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America.
2
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
3
Department of Population and Quantitative Heath Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
4
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
5
Department of Neurological Surgery and Institute of Human Genetics, School of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
6
Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
7
Institute for Clinical and Translational Research, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America.
8
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
9
School of Public Health, Yale University, New Haven, Connecticut, United States of America.
10
Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
11
Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, United States of America.
12
Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
13
Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
14
Oncology clinic, Finsen Center, Rigshospitalet, Copenhagen, Denmark.
15
Survivorship Research Unit, The Danish Cancer Society Research Center, Copenhagen, Denmark.
16
Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America.
17
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
18
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
19
Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
20
Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.
21
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
22
Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
23
Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
24
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
25
Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri, United States of America.
26
Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
27
Cancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, Arizona, United States of America.
28
Department of Radiation Sciences, Faculty of Medicine, Umeå University, Umeå, Sweden.
29
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
30
Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc, Gaithersburg, Maryland, United States of America.
31
Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America.
32
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America. jsb42@case.edu.

Abstract

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

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