Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA

Carcinogenesis. 2004 May;25(5):757-63. doi: 10.1093/carcin/bgh064. Epub 2004 Jan 16.

Abstract

We analysed the associations between genetic polymorphisms in genes coding for DNA repair enzymes XPD (exon 23 A --> C, K751Q), XPG (exon 15 G --> C, D1104H), XPC (exon 15 A --> C, K939Q), XRCC1 (exon 10 G --> A, R399Q) and XRCC3 (exon 7 C --> T, T241 M) and the levels of chromosomal aberrations (CAs) and single-strand breaks (SSBs) in peripheral lymphocytes in a central European population. We also measured the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines in these individuals. An elevated frequency of CAs was observed in individuals with the XPD exon 23 A allele (AA and AC) genotypes (F = 3.6, P = 0.028, ANOVA). In multifactorial analysis of variance, the XPD exon 23 polymorphism appeared as a major factor influencing CAs (F = 4.2, P = 0.017). SSBs in DNA, on the other hand, were modulated by XPD (F = 4.3, P = 0.023), XPG (F = 4.3, P = 0.024) and XRCC1 genotypes (F = 3.0, P = 0.064). Irradiation-specific DNA repair rates (reflecting mainly base excision repair activity) were affected by XRCC1 (F = 5.9, P = 0.010) and XPC polymorphisms (F = 4.2, P = 0.046, MANOVA). Our results from this study suggest that markers of genotoxicity are associated with polymorphisms in genes encoding DNA repair enzymes.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Aberrations*
  • Codon
  • DNA Damage / genetics*
  • DNA Helicases*
  • DNA Repair / genetics*
  • DNA, Single-Stranded / genetics*
  • DNA-Binding Proteins / genetics*
  • Endonucleases
  • Exons / genetics
  • Female
  • Humans
  • Male
  • Mutagenicity Tests
  • Nuclear Proteins
  • Polymorphism, Genetic*
  • Proteins / genetics
  • Transcription Factors*
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein

Substances

  • Codon
  • DNA excision repair protein ERCC-5
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proteins
  • Transcription Factors
  • X-ray Repair Cross Complementing Protein 1
  • X-ray repair cross complementing protein 3
  • XRCC1 protein, human
  • XPC protein, human
  • Endonucleases
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human