Skip to main content
SpringerLink
Log in

Cancer susceptibility variants and the risk of adult glioma in a US case–control study

  • Clinical Study – Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 01 February 2011

Abstract

Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case–control study. Cases were identified from neurosurgical and neuro-oncology clinics at major academic centers in the Southeastern US. Controls were identified from the community or were friends or other associates of cases. We examined a total of 191 susceptibility variants in genes identified in published cancer GWAS including glioma. A total of 639 glioma cases and 649 controls, all Caucasian, were included in analysis. Cases were enrolled a median of 1 month following diagnosis. Among glioma GWAS-identified variants, we detected associations in CDKN2B, RTEL1, TERT and PHLDB1, whereas we did not find overall associations for CCDC26. Results showed clear heterogeneity according to histologic subtypes of glioma, with TERT and RTEL variants a feature of astrocytic tumors and glioblastoma (GBM), CCDC26 and PHLDB1 variants a feature of astrocytic and oligodendroglial tumors, and CDKN2B variants most prominent in GBM. No examined variant in other cancer GWAS was found to be related to risk after adjustment for multiple comparisons. These results suggest that GWAS-identified SNPs in glioma mark different molecular etiologies in glioma. Stratification by broad histological subgroups may shed light on molecular mechanisms and assist in the discovery of novel loci in future studies of genetic susceptibility variants in glioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gu J, Liu Y, Kyritsis AP, Bondy ML (2009) Molecular epidemiology of primary brain tumors. Neurotherapeutics 6(3):427–435

    Article  PubMed  CAS  Google Scholar 

  2. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106(23):9362–9367

    Article  PubMed  CAS  Google Scholar 

  3. Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, LaChance DH, McCoy L, O’Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK (2009) Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 41(8):905–908

    Article  PubMed  CAS  Google Scholar 

  4. Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS ((2009)) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41(8):899–904

    Article  Google Scholar 

  5. Cardis E, Richardson L, Deltour I, Armstrong B, Feychting M, Johansen C, Kilkenny M, McKinney P, Modan B, Sadetzki S, Schüz J, Swerdlow A, Vrijheid M, Auvinen A, Berg G, Blettner M, Bowman J, Brown J, Chetrit A, Christensen HC, Cook A, Hepworth S, Giles G, Hours M, Iavarone I, Jarus-Hakak A, Klaeboe L, Krewski D, Lagorio S, Lönn S, Mann S, McBride M, Muir K, Nadon L, Parent ME, Pearce N, Salminen T, Schoemaker M, Schlehofer B, Siemiatycki J, Taki M, Takebayashi T, Tynes T, van Tongeren M, Vecchia P, Wiart J, Woodward A, Yamaguchi N (2007) The INTERPHONE study: design, epidemiological methods, and description of the study population. Eur J Epidemiol 22(9):647–664

    Article  PubMed  Google Scholar 

  6. Fang Z, Kulldorff M, Gregorio DI (2004) Brain cancer mortality in the United States, 1986–1995: a geographic analysis. Neuro Oncol 6:179–187

    Article  PubMed  Google Scholar 

  7. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) WHO classification of tumours of the central nervous system. IARC, Lyon

    Google Scholar 

  8. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 57:289–300

    Google Scholar 

  9. Verkhratsky A, Butt A (2007) Glial neurobiology. Wiley, Chichester, UK

    Book  Google Scholar 

  10. Liu Y, Shete S, Etzel CJ, Scheurer M, Alexiou G, Armstrong G, Tsavachidis S, Liang FW, Gilbert M, Aldape K, Armstrong T, Houlston R, Hosking F, Robertson L, Xiao Y, Wiencke J, Wrensch M, Andersson U, Melin BS, Bondy M (2010) Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict GBM survival. J Clin Oncol 28(14):2467–2474

    Article  PubMed  CAS  Google Scholar 

  11. Turnbull C, Rapley EA, Seal S, Pernet D, Renwick A, Hughes D, Ricketts M, Linger R, Nsengimana J, Deloukas P, Huddart RA, Bishop DT, Easton DF, Stratton MR, Rahman N (2010) UK testicular cancer collaboration. variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet 42(7):604–607

    Article  PubMed  CAS  Google Scholar 

  12. Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M, Mirabello L, Jacobs K, Wheeler W, Yeager M, Bergen AW, Li Q, Consonni D, Pesatori AC, Wacholder S, Thun M, Diver R, Oken M, Virtamo J, Albanes D, Wang Z, Burdette L, Doheny KF, Pugh EW, Laurie C, Brennan P, Hung R, Gaborieau V, McKay JD, Lathrop M, McLaughlin J, Wang Y, Tsao MS, Spitz MR, Wang Y, Krokan H, Vatten L, Skorpen F, Arnesen E, Benhamou S, Bouchard C, Metsapalu A, Vooder T, Nelis M, Välk K, Field JK, Chen C, Goodman G, Sulem P, Thorleifsson G, Rafnar T, Eisen T, Sauter W, Rosenberger A, Bickeböller H, Risch A, Chang-Claude J, Wichmann HE, Stefansson K, Houlston R, Amos CI, Fraumeni JF Jr, Savage SA, Bertazzi PA, Tucker MA, Chanock S, Caporaso NE (2009) A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet 85(5):679–691

    Article  PubMed  CAS  Google Scholar 

  13. Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS (2010) Role of 5p15.33 (TERT CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers. Carcinogenesis 31(2):234–238

    Article  PubMed  Google Scholar 

  14. McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njølstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubiñski J, Matyjasik J, Lener M, Oszutowska D, Field J, Liloglou T, Xinarianos G, Cassidy A, Study EPIC, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, González CA, Ramón Quirós J, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Kham KT, Key T, Bueno-de-Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P (2008) Lung cancer susceptibility locus at 5p15.33. Nat Genet 40(12):1404–1406

    Article  PubMed  CAS  Google Scholar 

  15. Liu H, Wang B, Han C (2010) Meta-analysis of genome-wide and replication association studies on prostate cancer. Prostate (in press)

  16. Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Björklund M, Wei G, Yan J, Niittymäki I, Mecklin JP, Järvinen H, Ristimäki A, Di-Bernardo M, East P, Carvajal-Carmona L, Houlston RS, Tomlinson I, Palin K, Ukkonen E, Karhu A, Taipale J, Aaltonen LA (2009) The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 41(8):885–890

    Article  PubMed  CAS  Google Scholar 

  17. Wokolorczyk D, Gliniewicz B, Sikorski A, Zlowocka E, Masojc B, Debniak T, Matyjasik J, Mierzejewski M, Medrek K, Oszutowska D, Suchy J, Gronwald J, Teodorczyk U, Huzarski T, Byrski T, Jakubowska A, Górski B, van de Wetering T, Walczak S, Narod SA, Lubinski J, Cybulski C (2008) A range of cancers is associated with the rs6983267 marker on chromosome 8. Cancer Res 68(23):9982–9986

    Article  PubMed  CAS  Google Scholar 

  18. Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Thomas G, Chanock SJ (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39(7):870–874

    Article  PubMed  CAS  Google Scholar 

  19. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human GBM genes and core pathways. Nature 455(7216):1061–1068

    Article  Google Scholar 

  20. Trembath D, Miller CR, Perry A (2008) Gray zones in brain tumor classification: evolving concepts. Adv Anat Pathol 15(5):287–297

    Article  PubMed  Google Scholar 

  21. Simon M, Hosking FJ, Marie Y, Gousias K, Boisselier B, Carpentier C, Schramm J, Mokhtari K, Hoang-Xuan K, Idbaih A, Delattre JY, Lathrop M, Robertson LB, Houlston RS, Sanson M (2010) Genetic risk profiles identify different molecular etiologies for glioma. Clin Cancer Res 16(21):5252–5259

    Article  PubMed  CAS  Google Scholar 

  22. Huse JT, Holland EC (2010) Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer 10(5):319–331

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge study participants for their contributions. We further wish to thank the clinicians and research staffs at participating medical centers. Special thanks go to Celia Sigua and Marek Wloch of the Tissue Core at Moffitt and Cara Sutcliffe of the Center for Human Genetics Research DNA Resources Core at Vanderbilt University School of Medicine for their work in processing DNA samples, and Ms. Anna Konidari and staff at the Center for Genome Technology at the Hussman Institute for Human Genomics, University of Miami for their expert technical assistance in the genotyping phase of the study. This study was supported by a grant from the National Institutes of Health (CA R01CA116174) as well as institutional funding from the Moffitt Cancer Center, Tampa, FL and the Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN.

Conflict of interest

The authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Cancer Epidemiology & Genetics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA

    Kathleen M. Egan, Melissa H. Madden, James E. Browning & Y. Ann Chen

  2. Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Reid C. Thompson

  3. Neuro-oncology Program, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    L. B. Nabors

  4. Department of Neurosurgery, Emory School of Medicine, Atlanta, GA, 30322, USA

    Jeffrey J. Olson

  5. Department of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, 30322, USA

    Daniel J. Brat

  6. Kentuckiana Cancer Institute, Louisville, KY, 40202, USA

    Renato V. LaRocca

  7. Department of Neurosurgery, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA

    Steven Brem

  8. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Paul L. Moots

  9. Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA

    Y. Ann Chen

Authors
  1. Kathleen M. Egan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reid C. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. B. Nabors
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey J. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel J. Brat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Renato V. LaRocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steven Brem
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paul L. Moots
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Melissa H. Madden
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. James E. Browning
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Y. Ann Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathleen M. Egan.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-011-0527-3

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLS 76 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Egan, K.M., Thompson, R.C., Nabors, L.B. et al. Cancer susceptibility variants and the risk of adult glioma in a US case–control study. J Neurooncol 104, 535–542 (2011). https://doi.org/10.1007/s11060-010-0506-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-010-0506-0

Keywords

Search

Navigation