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.

Details

Title
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
Ostrom, Quinn T 1 ; Kinnersley, Ben 2   VIAFID ORCID Logo  ; Wrensch, Margaret R 3 ; Eckel-Passow, Jeanette E 4 ; Armstrong, Georgina 5 ; Rice, Terri 3 ; Chen, Yanwen 6 ; Wiencke, John K 3 ; McCoy, Lucie S 3 ; Hansen, Helen M 3 ; Amos, Christopher I 7 ; Bernstein, Jonine L 8 ; Claus, Elizabeth B 9 ; Dora Il’yasova 10   VIAFID ORCID Logo  ; Johansen, Christoffer 11   VIAFID ORCID Logo  ; Lachance, Daniel H 12 ; Lai, Rose K 13 ; Merrell, Ryan T 14 ; Olson, Sara H 8 ; Siegal Sadetzki 15 ; Schildkraut, Joellen M 16 ; Shete, Sanjay 17 ; Rubin, Joshua B 18 ; Lathia, Justin D 19 ; Berens, Michael E 20   VIAFID ORCID Logo  ; Andersson, Ulrika 21 ; Rajaraman, Preetha 22 ; Chanock, Stephen J 23 ; Linet, Martha S 22 ; Wang, Zhaoming 23 ; Yeager, Meredith 23 ; Beane Freeman, Laura E 22 ; Koutros, Stella 22 ; Albanes, Demetrius 22 ; Visvanathan, Kala 24 ; Stevens, Victoria L 25 ; Henriksson, Roger 26 ; Michaud, Dominique S 27 ; Feychting, Maria 28 ; Ahlbom, Anders 28 ; Giles, Graham G 29 ; Milne, Roger 29 ; McKean-Cowdin, Roberta 30 ; Loic Le Marchand 31 ; Stampfer, Meir 32 ; Ruder, Avima M 33 ; Carreon, Tania 34 ; Hallmans, Göran 35 ; Zeleniuch-Jacquotte, Anne 36 ; Gaziano, J Michael 37 ; Sesso, Howard D 38 ; Purdue, Mark P 22 ; White, Emily 39 ; Peters, Ulrike 39 ; Buring, Julie 38 ; Houlston, Richard S 2 ; Jenkins, Robert B 40 ; Melin, Beatrice 21 ; Bondy, Melissa L 5 ; Barnholtz-Sloan, Jill S 6   VIAFID ORCID Logo 

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; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America; Department of Population and Quantitative Heath Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America 
2  Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom 
3  Department of Neurological Surgery and Institute of Human Genetics, School of Medicine, University of California, San Francisco, San Francisco, California, United States of America 
4  Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America 
5  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 
6  Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, 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; Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America 
10  Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, United States of America; Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America 
11  Oncology clinic, Finsen Center, Rigshospitalet, Copenhagen, Denmark; Survivorship Research Unit, The Danish Cancer Society Research Center, Copenhagen, Denmark 
12  Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America 
13  Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America 
14  Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, United States of America 
15  Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel 
16  Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America 
17  Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America 
18  Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri, United States of America 
19  Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America 
20  Cancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, Arizona, United States of America 
21  Department of Radiation Sciences, Faculty of Medicine, Umeå University, Umeå, Sweden 
22  Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America 
23  Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America; Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc, Gaithersburg, Maryland, United States of America 
24  Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America 
25  American Cancer Society, Atlanta, Georgia, United States of America 
26  Department of Oncology, Karolinska University Hospital, Stockholm, Sweden 
27  Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States of America 
28  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 
29  Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia 
30  Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America 
31  Department of Public Health, John A. Burns School of Medicine, University of Hawaii at Manoa, Manoma, Hawaii, United States of America 
32  Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America; Department of Epidemiology, Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America 
33  National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America 
34  Division of Surveillance, Hazard Evaluations, and Field Studies, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America 
35  Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Umeå, Sweden 
36  Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, New York, United States of America 
37  Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America 
38  Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America 
39  Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington, United States of America 
40  Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America 
Pages
1-15
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-24580-z
ProQuest document ID
2036771226
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.