Journal of Neuro-Oncology

, Volume 82, Issue 3, pp 229–237 | Cite as

Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma

  • Beatrice Susanne Malmer
  • Maria Feychting
  • Stefan Lönn
  • Sara Lindström
  • Henrik Grönberg
  • Anders Ahlbom
  • Judy Schwartzbaum
  • Anssi Auvinen
  • Helle Collatz-Christensen
  • Christoffer Johansen
  • Anne Kiuru
  • Nadejda Mudie
  • Tiina Salminen
  • Minouk J. Schoemaker
  • Anthony J. Swerdlow
  • Roger Henriksson
Laboratory Investigation

Abstract

Background

P53 and ATM are central checkpoint genes involved in the repair of DNA damage after ionising irradiation, which has been associated with risk of brain tumours. Therefore, we tested the hypothesis that polymorphisms and haplotypes in p53 and ATM could be associated with glioma and meningioma risk.

Material and Methods

Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program.

Results

The global statistical test of glioblastoma and p53 haplotypes was p = 0.02. The haplotype analysis on glioblastoma revealed the 1-2-2 haplotype (promotor-codon72-intron 6) had a frequency of 6.1% in cases compared with 9.8% in controls (p = 0.003).The 1-2-1 haplotype was significantly more frequent in GBM cases, 10.2%, than in controls, 7.3% (p = 0.02). The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype in meningioma cases (33.8%) compared with controls (30.3%) (p = 0.03). The 2-1-2-1-1 haplotype had a lower frequency in meningioma cases (36.1%) than controls (40.7%) (p = 0.009).

Conclusions

This study found both positive and negative associations of haplotypes in p53 for glioblastoma and ATM for meningioma. This study provides new data that could add to our understanding of brain tumour susceptibility.

Keywords

Brain tumour Cell cycle control Etiology 

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Beatrice Susanne Malmer
    • 1
  • Maria Feychting
    • 2
  • Stefan Lönn
    • 2
  • Sara Lindström
    • 1
  • Henrik Grönberg
    • 1
    • 3
  • Anders Ahlbom
    • 2
  • Judy Schwartzbaum
    • 2
    • 4
  • Anssi Auvinen
    • 5
    • 7
  • Helle Collatz-Christensen
    • 6
  • Christoffer Johansen
    • 6
  • Anne Kiuru
    • 7
  • Nadejda Mudie
    • 8
  • Tiina Salminen
    • 5
    • 7
  • Minouk J. Schoemaker
    • 8
  • Anthony J. Swerdlow
    • 8
  • Roger Henriksson
    • 1
  1. 1.Department of Radiation Sciences, OncologyUmeå University HospitalUmeåSweden
  2. 2.Institute of Environmental Medicine Karolinska InstitutetStockholmSweden
  3. 3.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  4. 4.Division of Epidemiology and Biometrics, School of Public HealthOhio State UniversityOhioUSA
  5. 5.Departments of Epidemiology, Tampere School of Public HealthUniversity of TampereTampereFinland
  6. 6.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  7. 7.Department of Research and Environmental SurveillanceSTUK-Radiation and Nuclear Safety AuthorityHelsinkiFinland
  8. 8.Section of EpidemiologyInstitute of Cancer ResearchSurreyUK

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