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

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.