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Rare microsatellite polymorphisms in the DNA repair genesXRCC1, XRCC3 andXRCC5 associated with cancer in patients of varying radiosensitivity

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Somatic Cell and Molecular Genetics

Abstract

DNA repair defects might contribute both to cancer progression and to the extreme reactions to radiotherapy observed in ≈5% of patients. Polymorphic microsatellites in three DNA repair genes, XRCC1, XRCC3 and XRCC5, were analyzed for possible linkage to cancer status or clinical radiosensitivity. XRCC1, 3 and 5 proteins are involved in single-strand DNA break rejoining, recombinational repair, and double-strand DNA break rejoining respectively. Mendelianly inherited microsatellite polymorphisms in these genes were analyzed in three groups: volunteers with no cancer history; radiosensitive cancer patients; cancer patients with acceptable reactions to radiotherapy. Rare heterozygous alterations in all three gene regions were found solely in the cancer subpopulation. Association testing between these rare polymorphisms and cancer status revealed a significant association for XRCC1 (P=0.005), and XRCC3 (P=0.004). There was also an association between these polymorphisms and clinical radiosensitivity for XRCC1 (P=0.03), and XRCC3 (P=0.005).

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Authors and Affiliations

  1. Human Molecular Genetics Group, Department of Biology and Biochemistry, Brunel University, UB8 3PH, Uxbridge, Middlesex, UK

    E. A. Price & J. E. Arrand

  2. Gray Laboratory, Mount Vernon Hospital, HA6 2JR, Northwood, Middlesex, UK

    S. L. Bourne

  3. The Mount Vernon Centre for Cancer Treatment, Mount Vernon

    P. A. Lawton

  4. Watford Hospitals, NHS Trust, HA6 2RN, Northwood, Middlesex, UK

    J. Lamerdin

  5. Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, 94551, Livermore, California

    L. H. Thompson

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  1. E. A. Price
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  3. R. Radbourne
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Price, E.A., Bourne, S.L., Radbourne, R. et al. Rare microsatellite polymorphisms in the DNA repair genesXRCC1, XRCC3 andXRCC5 associated with cancer in patients of varying radiosensitivity. Somat Cell Mol Genet 23, 237–247 (1997). https://doi.org/10.1007/BF02674415

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  • DOI: https://doi.org/10.1007/BF02674415

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