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

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

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Acknowledgments

All centres were supported by the European Union Fifth Framework Program “Quality of life and Management of Living Resources” (contract number QLK4-CT-1999-01563), and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by agreements that guaranteed INTERPHONE’s complete scientific independence. These agreements are publicly available at http://www.iarc.fr/ENG/Units/RCAd.html. The Swedish centre was also supported by the Swedish Research Council, the Cancer Foundation of Northern Sweden, the Swedish Cancer Society, and the Nordic Cancer Union. The Danish centre was supported by the Danish Cancer Society, the Finnish centre by the Emil Aaltonen Foundation and the Academy of Finland, The Cancer Society of Finland, and the UK centre by the Mobile Telecommunications and Health Research (MTHR) Programme. We also thank all patients, interviewers and team collaborators in the study in all participating countries.

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Authors and Affiliations

  1. Department of Radiation Sciences, Oncology, Umeå University Hospital, 901 85, Umeå, Sweden

    Beatrice Susanne Malmer, Sara Lindström, Henrik Grönberg & Roger Henriksson

  2. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Maria Feychting, Stefan Lönn, Anders Ahlbom & Judy Schwartzbaum

  3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Henrik Grönberg

  4. Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Ohio, Buckeye, USA

    Judy Schwartzbaum

  5. Departments of Epidemiology, Tampere School of Public Health, University of Tampere, Tampere, Finland

    Anssi Auvinen & Tiina Salminen

  6. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark

    Helle Collatz-Christensen & Christoffer Johansen

  7. Department of Research and Environmental Surveillance, STUK-Radiation and Nuclear Safety Authority, Helsinki, Finland

    Anssi Auvinen, Anne Kiuru & Tiina Salminen

  8. Section of Epidemiology, Institute of Cancer Research, Surrey, UK

    Nadejda Mudie, Minouk J. Schoemaker & Anthony J. Swerdlow

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  1. Beatrice Susanne Malmer
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  2. Maria Feychting
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Correspondence to Beatrice Susanne Malmer.

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Malmer, B.S., Feychting, M., Lönn, S. et al. Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma. J Neurooncol 82, 229–237 (2007). https://doi.org/10.1007/s11060-006-9275-1

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  • DOI: https://doi.org/10.1007/s11060-006-9275-1

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