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Human Genetics

, Volume 131, Issue 9, pp 1507–1517 | Cite as

Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

  • Yanhong Liu
  • Beatrice S. Melin
  • Preetha Rajaraman
  • Zhaoming Wang
  • Martha Linet
  • Sanjay Shete
  • Christopher I. Amos
  • Ching C. Lau
  • Michael E. Scheurer
  • Spiridon Tsavachidis
  • Georgina N. Armstrong
  • Richard S. Houlston
  • Fay J. Hosking
  • Elizabeth B. Claus
  • Jill Barnholtz-Sloan
  • Rose Lai
  • Dora Il’yasova
  • Joellen Schildkraut
  • Siegal Sadetzki
  • Christoffer Johansen
  • Jonine L. Bernstein
  • Sara H. Olson
  • Robert B. Jenkins
  • Daniel LaChance
  • Nicholas A. Vick
  • Margaret Wrensch
  • Faith Davis
  • Bridget J. McCarthy
  • Ulrika Andersson
  • Patricia A. Thompson
  • Stephen Chanock
  • The Gliogene Consortium
  • Melissa L. BondyEmail author
Original Investigation

Abstract

The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10−8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

Keywords

Primary Brain Tumor Glioma Risk Glioma Case Nerve Growth Factor Signal Plausible Candidate Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

PBT

Primary brain tumor

SNP

Single nucleotide polymorphism

GWA

Genome-wide association

LD

Linkage disequilibrium

LOD

Logarithm (base 10) of odds

OR

Odds ratio

CI

95 % confidence interval

Notes

Acknowledgments

This work was supported by National Institutes of Health (5R01 CA119215, 5R01 CA070917 and R01CA52689). Additional support was provided by the American Brain Tumor Association, The National Brain Tumor Society, the Tug McGraw Foundation and the Wellcome Trust who provided funding for the parent GWAS. The authors acknowledge the input of the Gliogene External Advisory Committee. For more information about the Gliogene Consortium, please refer to the following Web site http://www.gliogene.org.

Conflict of interest

None declared.

Supplementary material

439_2012_1187_MOESM1_ESM.pdf (61 kb)
Supplementary material 1 (PDF 60.6 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Yanhong Liu
    • 1
  • Beatrice S. Melin
    • 20
  • Preetha Rajaraman
    • 3
  • Zhaoming Wang
    • 3
  • Martha Linet
    • 3
  • Sanjay Shete
    • 4
  • Christopher I. Amos
    • 5
  • Ching C. Lau
    • 2
  • Michael E. Scheurer
    • 1
  • Spiridon Tsavachidis
    • 1
  • Georgina N. Armstrong
    • 1
  • Richard S. Houlston
    • 6
  • Fay J. Hosking
    • 6
  • Elizabeth B. Claus
    • 7
    • 8
  • Jill Barnholtz-Sloan
    • 9
  • Rose Lai
    • 10
  • Dora Il’yasova
    • 11
  • Joellen Schildkraut
    • 11
  • Siegal Sadetzki
    • 12
    • 13
  • Christoffer Johansen
    • 14
  • Jonine L. Bernstein
    • 15
  • Sara H. Olson
    • 15
  • Robert B. Jenkins
    • 16
  • Daniel LaChance
    • 16
  • Nicholas A. Vick
    • 17
  • Margaret Wrensch
    • 18
  • Faith Davis
    • 19
  • Bridget J. McCarthy
    • 19
  • Ulrika Andersson
    • 20
  • Patricia A. Thompson
    • 21
  • Stephen Chanock
    • 3
  • The Gliogene Consortium
  • Melissa L. Bondy
    • 1
    Email author
  1. 1.Dan L. Duncan Cancer CenterBaylor College of MedicineHoustonUSA
  2. 2.Department of PediatricsBaylor College of MedicineHoustonUSA
  3. 3.Division of Cancer Epidemiology and Genetics, Department Health and Human ServicesNational Cancer Institute, National Institutes of HealthBethesdaUSA
  4. 4.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of GeneticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Division of Genetics and EpidemiologyInstitute of Cancer ResearchSuttonUK
  7. 7.Department of Epidemiology and Public HealthYale University School of MedicineNew HavenUSA
  8. 8.Department of NeurosurgeryBrigham and Women’s HospitalBostonUSA
  9. 9.Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandUSA
  10. 10.The Neurological Institute of Columbia UniversityNew YorkUSA
  11. 11.Cancer Control and Prevention Program, Department of Community and Family MedicineDuke University Medical CenterDurhamUSA
  12. 12.Cancer and Radiation Epidemiology Unit, Chaim Sheba Medical CenterGertner InstituteTel HashomerIsrael
  13. 13.Sackler School of MedicineTel-Aviv UniversityTel AvivIsrael
  14. 14.Department of NeurologyDanish Cancer SocietyCopenhagenDenmark
  15. 15.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  16. 16.Mayo Clinic Comprehensive Cancer CenterMayo ClinicRochesterUSA
  17. 17.Evanston Kellogg Cancer Care Center, North Shore University Health SystemEvanstonUSA
  18. 18.Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA
  19. 19.Division of Epidemiology and BiostatisticsUniversity of Illinois at ChicagoChicagoUSA
  20. 20.Department of Radiation Sciences OncologyUmeå UniversityUmeåSweden
  21. 21.Arizona Cancer CenterUniversity of ArizonaTucsonUSA

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