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XRCC1 and XRCC3 variants and risk of glioma and meningioma

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Abstract

Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case–control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97–1.81), glioblastoma (OR = 1.48; 95% CI, 0.98–2.24), and meningioma (OR = 1.34; 95% CI, 0.96–1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26–8.04) and meningioma (OR = 2.99; 95% CI, 1.16–7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

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Acknowledgements

The authors warmly thank all patients, controls, interviewers, and team collaborators in the study in all the participating countries, as listed in Lahkola et al. [25] for their invaluable contribution to this work. This research was supported by a grant from the Nordic Cancer Union. The INTERPHONE Study was supported by the European Commission Fifth Framework Program “Quality of Life and Management of Living Resources” (contract number QLK4-CT-1999–01563), and the International Union against Cancer (UICC; RCA/01/08). The UICC received funds for this study from the Mobile Manufacturers’ Forum and the Global System for Mobile Communications 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 INTERPHONE site (2005) (International Agency for Research on Cancer. http://www.iarc.fr/ENG/Units/RCAd.html). Additional support was given by the Academy of Finland (grant number 71037), the Cancer Foundation of Northern Sweden, the Cancer Society of Finland, the Danish Cancer Society, the Emil Aaltonen Foundation, the Mobile Telecommunications and Health Research (MTHR) Program, the Swedish Cancer Society, and the Swedish Research Council. The views expressed in this paper are not necessarily those of the funders.

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Authors and Affiliations

  1. Department of Research and Environmental Surveillance, STUK-Radiation and Nuclear Safety Authority, Box 14, 00881, Helsinki, Finland

    Anne Kiuru, Carita Lindholm, Sirpa Heinävaara, Taina Ilus, Päivi Jokinen & Anssi Auvinen

  2. Department of Pathology, Centre for Laboratory Medicine, Tampere University Hospital, Box 2000, 33520, Tampere, Finland

    Hannu Haapasalo

  3. Department of Epidemiology, Tampere School of Public Health, University of Tampere, 33014, Tampere, Finland

    Tiina Salminen & Anssi Auvinen

  4. Department of Psychosocial Cancer Research, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100, Copenhagen, Denmark

    Helle Collatz Christensen & Christoffer Johansen

  5. Division of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177, Stockholm, Sweden

    Maria Feychting & Stefan Lönn

  6. Department of Radiation Sciences, Oncology, Umeå University Hospital, 90185, Umea, Sweden

    Beatrice Malmer

  7. Section of Epidemiology, Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG, UK

    Minouk J. Schoemaker & Anthony J. Swerdlow

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  1. Anne Kiuru
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  2. Carita Lindholm
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  11. Stefan Lönn
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  15. Anssi Auvinen
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Correspondence to Anne Kiuru.

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Kiuru, A., Lindholm, C., Heinävaara, S. et al. XRCC1 and XRCC3 variants and risk of glioma and meningioma. J Neurooncol 88, 135–142 (2008). https://doi.org/10.1007/s11060-008-9556-y

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  • DOI: https://doi.org/10.1007/s11060-008-9556-y

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