Prevention and Epidemiology Genome-Wide High-Density SNP Linkage Search for Glioma Susceptibility Loci: Results from the Gliogene Consortium

Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P 1⁄4 0.0005) at 17q12-21.32 Authors' Affiliations: Department of Epidemiology, The University of Texas MD Anderson Cancer Center; Department of Pediatrics, Division ofHematology-Oncology, Dan L. DuncanCancer Center, Baylor College of Medicine, Houston, Texas; Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom; Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut; Department of Neurosurgery, Brigham and Women's Hospital, Boston,Massachusetts; CaseComprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; The Neurological Institute of Columbia University; Department of Epidemiology and Biostatistics, Memorial Sloan-KetteringCancer Center; NewYork, New York; Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina; Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim ShebaMedical Center, Tel Hashomer; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Neurology; Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota; Department of Radiation Sciences Oncology, Umea University, Umea , Sweden; Evanston Kellogg Cancer Care Center NorthShore University HealthSystem, Evanston, Illinois; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California; and Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois Themembersof theGliogeneConsortium:DepartmentofEpidemiology,The University of Texas MD Anderson Cancer Center, Houston, Texas (Sanjay Shete, Robert K. Yu); Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas (Christopher Amos); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Kenneth D. Aldape); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Mark R. Gilbert); Department ofNeurosurgery, TheUniversityof TexasMDAnderson Cancer Center, Houston, Texas (Jeffrey Weinberg); Department of Pediatrics, Section of Hematology and Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas (Ching C. Lau, Eastwood Honchiu Leung, Caleb Davis, Rita Cheng, Chris Man, Rudy Guerra, SivashankarappaGurusiddappa,Michael E. Scheurer,MelissaL.Bondy,GeorginaN. Armstrong, Yanhong Liu); Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom (Richard S. Houlston, Fay J. Hosking, Lindsay Robertson, Elli Papaemmanuil); Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut (ElizabethB.Claus);Department ofNeurosurgery,Brighamand Women'sHospital,Boston,Massachusetts (ElizabethB.Claus);CaseComprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio (Jill Barnholtz-Sloan, Andrew E. Sloan, Gene Barnett,KarenDevine,YingliWolinsky); TheNeurological InstituteofColumbia University, New York, New York (Rose Lai, Erika Florendo, Delcia Rivas, Christina Corpuz); Cancer Control and Prevention Program, Department of Community and FamilyMedicine, DukeUniversityMedical Center, Durham, North Carolina (Dora Il'yasova, Joellen Schildkraut); Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel (Siegal Sadetzki, Galit Hirsh Yechezkel, Revital Bar-Sade Bruchim, Lili Aslanov); Sackler School of Medicine, Tel-Aviv University, TelAviv, Israel (Siegal Sadetzki); Department of Neurology; Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (Christoffer Johansen, Hanne Bødtcher); Neurosurgery Department, Rigshospitalet, University Copenhagen (Michael Kosteljanetz), Neuropathology Department, Rigshospitalet, University Copenhagen (Helle Broholm); Department ofEpidemiologyandBiostatistics,MemorialSloan-KetteringCancerCenter, New York, New York (Jonine L. Bernstein, Sara H. Olson, Erica Schubert), Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (Lisa DeAngelis); Mayo Clinic Comprehensive Cancer Center,Mayo Clinic, Rochester, Minnesota (Robert B. Jenkins, Ping Yang, Amanda Rynearson); Department of Radiation Sciences Oncology, Umea University, Umea , Sweden (Beatrice S. Melin, Roger Henriksson, Ulrika Andersson), Department of Medical Biosciences, Umea University, Umea , Sweden (Thomas Br€ annstr€ om); Evanston Kellogg Cancer Care Center, North Shore University Health System, Evanston, Illinois (Nicholas A. Vick); Departments of Neurological Surgery and Epidemiology and Biostatistics (Margaret Wrensch, John Wiencke, Joe Wiemels, Lucie McCoy) Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois (Bridget J. McCarthy, Faith G. Davis). Note: Sanjay Shete, Ching C. Lau, Richard S. Houlston, Beatrice S. Melin, and Melissa L. Bondy contributed equally to this work. Corresponding Authors: Sanjay Shete, and Melissa Bondy, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1340, Houston, TX 77030. Phone: 713-7453020; Fax: 713-792-8261; E-mail: [email protected] and [email protected] doi: 10.1158/0008-5472.CAN-11-0013 2011 American Association for Cancer Research. Cancer Research www.aacrjournals.org OF1 Research. on April 12, 2017. © 2011 American Association for Cancer cancerres.aacrjournals.org Downloaded from Published OnlineFirst October 28, 2011; DOI: 10.1158/0008-5472.CAN-11-0013