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Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas

  • Clinical Study – Patient Study
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Abstract

The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054–0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.

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Acknowledgments

The Swedish centre was supported by the Swedish Research Council, the Cancer Foundation of Northern Sweden, The Cancer Foundation at the Uppsala University Hospital, the Swedish Cancer Society, and The Nordic Cancer Union and The Umeå University Hospital Excellence grant and Young career research reward at Umeå University. Melin was supported by Acta Oncologica through the Royal Swedish Academy of Science. The Danish centre was supported by the Danish Cancer Society. The cases were identified through the Interphone study and 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/en/research-groups/RAD/RCAd.html. We are grateful to all patients and individuals for their participation. We would also like to thank the clinicians and other hospital staff, cancer registries and study staff and the funding bodies who contributed to the blood sample and data collection for this study and who are listed in our previous publications. The views expressed in the publication are those of the authors and not necessarily those of the funding bodies.

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Authors and Affiliations

  1. Department of Neuroscience, Neurology, University Hospital, 75185, Uppsala, Sweden

    Shala Ghaderi Berntsson, Shala Ghaderi Berntsson & Anja Smits

  2. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

    Carl Wibom, Sara Sjöström, Roger Henriksson, Ulrika Andersson & Beatrice S. Melin

  3. Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden

    Carl Wibom

  4. Stockholm Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden

    Roger Henriksson

  5. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

    Thomas Brännström

  6. Department of Pathology, The Centre of Diagnostic Investigations, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Helle Broholm

  7. ENT Department, University Hospital of Copenhagen, Hellerup, Denmark

    Christoffer Johansson

  8. Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, UK

    Sarah J. Fleming & Patricia A. McKinney

  9. Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK

    Lara Bethke & Richard Houlston

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  1. Shala Ghaderi Berntsson
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Correspondence to Shala Ghaderi Berntsson.

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Berntsson, S.G., Wibom, C., Sjöström, S. et al. Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas. J Neurooncol 105, 531–538 (2011). https://doi.org/10.1007/s11060-011-0614-5

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