Human Genetics

, Volume 131, Issue 12, pp 1877–1888

Genome-wide association study of glioma and meta-analysis

  • Preetha Rajaraman
  • Beatrice S. Melin
  • Zhaoming Wang
  • Roberta McKean-Cowdin
  • Dominique S. Michaud
  • Sophia S. Wang
  • Melissa Bondy
  • Richard Houlston
  • Robert B. Jenkins
  • Margaret Wrensch
  • Meredith Yeager
  • Anders Ahlbom
  • Demetrius Albanes
  • Ulrika Andersson
  • Laura E. Beane Freeman
  • Julie E. Buring
  • Mary Ann Butler
  • Melissa Braganza
  • Tania Carreon
  • Maria Feychting
  • Sarah J. Fleming
  • Susan M. Gapstur
  • J. Michael Gaziano
  • Graham G. Giles
  • Goran Hallmans
  • Roger Henriksson
  • Judith Hoffman-Bolton
  • Peter D. Inskip
  • Christoffer Johansen
  • Cari M. Kitahara
  • Mark Lathrop
  • Chenwei Liu
  • Loic Le Marchand
  • Martha S. Linet
  • Stefan Lonn
  • Ulrike Peters
  • Mark P. Purdue
  • Nathaniel Rothman
  • Avima M. Ruder
  • Marc Sanson
  • Howard D. Sesso
  • Gianluca Severi
  • Xiao-Ou Shu
  • Matthias Simon
  • Meir Stampfer
  • Victoria L. Stevens
  • Kala Visvanathan
  • Emily White
  • Alicja Wolk
  • Anne Zeleniuch-Jacquotte
  • Wei Zheng
  • Paul Decker
  • Victor Enciso-Mora
  • Brooke Fridley
  • Yu-Tang Gao
  • Matthew Kosel
  • Daniel H. Lachance
  • Ching Lau
  • Terri Rice
  • Anthony Swerdlow
  • Joseph L. Wiemels
  • John K. Wiencke
  • Sanjay Shete
  • Yong-Bing Xiang
  • Yuanyuan Xiao
  • Robert N. Hoover
  • Joseph F. FraumeniJr.
  • Nilanjan Chatterjee
  • Patricia Hartge
  • Stephen J. Chanock
Original Investigation

DOI: 10.1007/s00439-012-1212-0

Cite this article as:
Rajaraman, P., Melin, B.S., Wang, Z. et al. Hum Genet (2012) 131: 1877. doi:10.1007/s00439-012-1212-0

Abstract

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case–control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case–control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Supplementary material

439_2012_1212_MOESM1_ESM.doc (127 kb)
Supplementary material 1 (DOCX 129 kb)
439_2012_1212_MOESM2_ESM.doc (17 kb)
Supplementary material 2 (DOC 33 kb)

Copyright information

© Springer-Verlag (outside the USA) 2012

Authors and Affiliations

  • Preetha Rajaraman
    • 1
    • 40
  • Beatrice S. Melin
    • 2
  • Zhaoming Wang
    • 1
    • 3
  • Roberta McKean-Cowdin
    • 4
  • Dominique S. Michaud
    • 5
    • 6
  • Sophia S. Wang
    • 7
  • Melissa Bondy
    • 8
  • Richard Houlston
    • 9
  • Robert B. Jenkins
    • 10
  • Margaret Wrensch
    • 11
  • Meredith Yeager
    • 1
    • 3
  • Anders Ahlbom
    • 12
  • Demetrius Albanes
    • 1
  • Ulrika Andersson
    • 2
  • Laura E. Beane Freeman
    • 1
  • Julie E. Buring
    • 13
  • Mary Ann Butler
    • 14
  • Melissa Braganza
    • 1
  • Tania Carreon
    • 14
  • Maria Feychting
    • 12
  • Sarah J. Fleming
    • 15
  • Susan M. Gapstur
    • 16
  • J. Michael Gaziano
    • 13
    • 17
  • Graham G. Giles
    • 18
    • 19
  • Goran Hallmans
    • 20
  • Roger Henriksson
    • 2
  • Judith Hoffman-Bolton
    • 21
  • Peter D. Inskip
    • 1
  • Christoffer Johansen
    • 22
  • Cari M. Kitahara
    • 1
  • Mark Lathrop
    • 23
    • 24
  • Chenwei Liu
    • 3
  • Loic Le Marchand
    • 25
  • Martha S. Linet
    • 1
  • Stefan Lonn
    • 12
    • 26
  • Ulrike Peters
    • 27
    • 28
  • Mark P. Purdue
    • 1
  • Nathaniel Rothman
    • 1
  • Avima M. Ruder
    • 14
  • Marc Sanson
    • 29
  • Howard D. Sesso
    • 13
  • Gianluca Severi
    • 18
    • 19
  • Xiao-Ou Shu
    • 30
  • Matthias Simon
    • 31
  • Meir Stampfer
    • 32
    • 33
  • Victoria L. Stevens
    • 16
  • Kala Visvanathan
    • 21
    • 34
  • Emily White
    • 27
    • 28
  • Alicja Wolk
    • 35
  • Anne Zeleniuch-Jacquotte
    • 36
  • Wei Zheng
    • 30
  • Paul Decker
    • 10
  • Victor Enciso-Mora
    • 9
  • Brooke Fridley
    • 10
  • Yu-Tang Gao
    • 37
  • Matthew Kosel
    • 10
  • Daniel H. Lachance
    • 10
  • Ching Lau
    • 8
  • Terri Rice
    • 11
  • Anthony Swerdlow
    • 9
    • 38
  • Joseph L. Wiemels
    • 11
  • John K. Wiencke
    • 11
  • Sanjay Shete
    • 39
  • Yong-Bing Xiang
    • 37
  • Yuanyuan Xiao
    • 11
  • Robert N. Hoover
    • 1
  • Joseph F. FraumeniJr.
    • 1
  • Nilanjan Chatterjee
    • 1
  • Patricia Hartge
    • 1
  • Stephen J. Chanock
    • 1
    • 3
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleUSA
  2. 2.Department of Radiation Sciences, OncologyUmeå UniversityUmeåSweden
  3. 3.Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, IncGaithersburgUSA
  4. 4.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Division of Biology and Medicine, Department of EpidemiologyBrown UniversityProvidenceUSA
  6. 6.School of Public Health, Imperial College LondonLondonUK
  7. 7.Division of Cancer Etiology, Department of Population SciencesCity of Hope and the Beckman Research InstituteDuarteUSA
  8. 8.Baylor College of MedicineHoustonUSA
  9. 9.Division of Genetics and EpidemiologyInstitute of Cancer ResearchSuttonUK
  10. 10.Mayo ClinicRochesterUSA
  11. 11.University of California San FranciscoSan FranciscoUSA
  12. 12.Division of Epidemiology, Institute of Environmental MedicineKarolinska InstitutetStockholmSweden
  13. 13.Division of Preventive MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  14. 14.National Institute for Occupational Safety and HealthCenters for Disease Control and PreventionCincinnatiUSA
  15. 15.Division of BiostatisticsUniversity of LeedsLeedsUK
  16. 16.Epidemiology Research Program, American Cancer SocietyAtlantaUSA
  17. 17.Massachusetts Veteran’s Epidemiology, Research and Information Center, Geriatric Research Education and Clinical CenterVA Boston Healthcare SystemBostonUSA
  18. 18.Cancer Epidemiology Centre, Cancer Council of VictoriaMelbourneAustralia
  19. 19.Centre for Molecular, Environmental, Genetic, and Analytic EpidemiologyUniversity of MelbourneMelbourneAustralia
  20. 20.Department of Public Health and Clinical Medicine/Nutritional ResearchUmeå UniversityUmeåSweden
  21. 21.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  22. 22.Unit of SurvivorshipThe Danish Cancer Society Research CenterCopenhagenDenmark
  23. 23.Centre National de Genotypage, IG/CEAEvry CedexFrance
  24. 24.Foundation Jean Dauset-CEPHParisFrance
  25. 25.Cancer Research CenterUniversity of HawaiiHonoluluUSA
  26. 26.Medical Department, AstraZeneca NordicSödertäljeSweden
  27. 27.Fred Hutchinson Cancer Research CenterSeattleUSA
  28. 28.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  29. 29.Service de Neurologie Mazarin, GH Pitié-Salpêtrière, APHP, and UMR 975 INSERM-UPMC, CRICMParisFrance
  30. 30.Vanderbilt University Medical CenterNashvilleUSA
  31. 31.Neurochirurgische UniversitatsklinikBonnGermany
  32. 32.Channing LaboratoryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  33. 33.Departments of Epidemiology and NutritionHarvard School of Public HealthBostonUSA
  34. 34.Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimoreUSA
  35. 35.Division of Nutritional EpidemiologyInstitute of Environmental Medicine, Karolinska InstitutetStockholmSweden
  36. 36.Division of Epidemiology, Department of Environmental MedicineNYU School of MedicineNew YorkUSA
  37. 37.Department of Epidemiology, Shanghai Cancer Institute, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  38. 38.Division of Breast Cancer ResearchInstitute of Cancer ResearchLondonUK
  39. 39.Department of BiostatisticsMD Anderson Cancer CenterOrlandoUSA
  40. 40.Radiation Epidemiology Branch, Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA