Year: 2018
Type: article
Abstract: Background: To date, genome-wide association studies (GWAS) have identified 25 risk variants for glioma, explaining 30% of heritable risk. Most histologies occur with significantly higher incidence in males, and this difference is not explained by currently known risk factors. A previous GWAS identified sex-specific glioma risk variants, and this analysis aims to further elucidate risk variation by sex using gene- and pathway-based approaches. Methods: Results from the Glioma International Case-Control Study were used as a testing set, and results from 3 GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for nominally significant autosomal SNPs (P < 0.01 in a previous meta-analysis) and nominally significant X-chromosome SNPs (P < 0.01), 3 algorithms (Pascal, BimBam, and GATES) were used to generate gene scores, and Pascal was used to generate pathway scores. Results were considered statistically significant in the discovery set when P < 3.3 × 10-6 and in the validation set when P < 0.001 in 2 of 3 algorithms. Results: Twenty-five genes within 5 regions and 19 genes within 6 regions reached statistical significance in at least 2 of 3 algorithms in males and females, respectively. EGFR was significantly associated with all glioma and glioblastoma in males only and a female-specific association in TERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the BioCarta telomeres pathway in both males and females. Conclusions: These results provide additional evidence that there may be differences by sex in genetic risk for glioma. Additional analyses may further elucidate the biological processes through which this risk is conferred.
Source: Neuro-Oncology
Authors: Quinn T Ostrom, Warren Coleman, William Huang, Joshua B Rubin, Justin D Lathia, Michael E Berens, Gil Speyer, Peter Liao, Margaret R Wrensch, Jeanette E Eckel-Passow, Georgina Armstrong, Terri Rice, John K Wiencke, Lucie S McCoy, Helen M Hansen, Christopher I Amos, Jonine L Bernstein, Elizabeth B Claus, Richard S Houlston, Dora Il’yasova, Robert B Jenkins, Christoffer Johansen, Daniel H Lachance, Rose K Lai, Ryan T Merrell, Sara H Olson, Siegal Sadetzki, Joellen M Schildkraut, Sanjay Shete, Ulrika Andersson, Preetha Rajaraman, Stephen J Chanock, Martha S Linet, Zhaoming Wang, Meredith Yeager, M Berger, P Bracci, S Chang, J Clarke, A Molinaro, A Perry, M Pezmecki, M Prados, I Smirnov, T Tihan, K Walsh, J Wiemels, S Zheng, Laura E Beane Freeman, Stella Koutros, Demetrius Albanes, Kala Visvanathan, Victoria L Stevens, Roger Henriksson, Dominique S Michaud, Maria Feychting, Anders Ahlbom, Graham G Giles Roger Milne, Roberta McKean-Cowdin, Loic Le Marchand, Meir Stampfer, Avima M Ruder, Tania Carreon, Goran Hallmans, Anne Zeleniuch-Jacquotte, J Michael Gaziano, Howard D Sesso, Mark P Purdue, Emily White, Ulrike Peters, Julie Buring, Beatrice Melin, Melissa L Bondy, Jill S Barnholtz-Sloan
Institutions: Baylor College of Medicine, Case Comprehensive Cancer Center, Dan L Duncan Comprehensive Cancer Center, Case Western Reserve University, University School, Washington University in St. Louis, Cleveland Clinic, Translational Genomics Research Institute, University of California, San Francisco, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Brigham and Women's Hospital, Yale University, Institute of Cancer Research, Duke University, Georgia State University, Duke Medical Center, Duke Cancer Institute, Mayo Clinic Comprehensive Cancer Center (Minnesota), Rigshospitalet, Danish Cancer Society, University of Southern California, Endeavor Health, The University of Texas MD Anderson Cancer Center, Tel Aviv University, Sheba Medical Center, University of Virginia, Umeå University, Division of Cancer Epidemiology and Genetics, National Cancer Institute, St. Jude Children's Research Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Robert and Janice McNair Foundation, Cancer Prevention and Research Institute of Texas, California Department of Public Health, University of Southern California, Purdue University, Baylor College of Medicine, Wellcome Trust, Swedish Cancer Foundation, Vetenskapsrådet, National Institutes of Health, Centers for Disease Control and Prevention, University of California, San Francisco, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources, National Center for Chronic Disease Prevention and Health Promotion, National Center for Advancing Translational Sciences
Awards: G1289825209, G1311563309, G1393855433, G1436032867, Clinical and Translational Science Institute, G1686243375, G2089898225, G2232313487, G2238803135, G22827645, G2312670204, G2434515398, G2612351997, G2639781304, G2690160998, G2964610485, G3014186981, G3123501928, G3161224617, G3190882026, G3509688676, The NYU Women's Health Study, G418187648, G4203349661, G4321129689, G4322373146, G4375562889, G4393609197, G4428815567, G4527459645, G480705112, International Case Control Study of Malignant Glioma, G4959201785, G532587972, G5333917095, G5433357946, CALIFORNIA COORDINATED CANCER PREVENTION & CONTROL PROGRAM, G5570217171, Immune epigenetic biomarkers of survival in glioma epidemiology, G558664196, G5731374235, G6232100115, G6362444212, G6793263369, G6795547015, G6927604221, G69825400, G7195422766, G7452499634, G758528517, G7693998277, G7763339852, G793654858, G8247152613, G835000939, G8923144227, G9000045896, G9000058261, G9000201119, G9000344134, Cancer Center Support Grant, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, G937853209
OpenAlex ID: W2784799660