The cell's susceptibility to DNA damage and its ability to repair this damage are important for
cancer induction, promotion and progression. In the present work we determined the level of basal (total endogenous) and endogenous oxidative DNA damage as well as polymorphism of the DNA repair genes: RAD51 (135 G/C), XRCC3 (Thr241Met), OGG1 (Ser326Cys) and XPD (Lys751Gln) in peripheral blood lymphocytes of 41
breast cancer patients and 48 healthy individuals. DNA damage was evaluated by alkaline comet assay with
DNA repair enzymes: Endo III and Fpg, preferentially recognizing oxidized
DNA bases. The genotypes of the polymorphisms were determined by restriction fragment length polymorphism PCR. We observed a strong association between
breast cancer occurrence and the genotypes C/C of the RAD51-135G/C polymorphism, Ser/Ser of the OGG1-Ser326Cys and Lys/Gln of the XPD-Lys751Gln, whereas the genotypes G/C of the RAD51-135G/C and
Lys/Lys of the XPD-Lys751Gln exerted a protective effect against
breast cancer. We also found that individuals with the G/C genotype of the RAD51-135G/C polymorphism and with the
Lys/Lys genotype of the XPD-Lys751Gln polymorphism displayed a lower extent of basal and oxidative DNA damage. A strong association between higher level of oxidative DNA damage and the Lys/Gln genotype of the latter polymorphism was found. We also correlated genotypes with clinical characteristics of
breast cancer patients. We observed a strong association between the G/C genotype of the RAD51-135 G/C polymorphism and the expression of the
progesterone receptor and between both alleles of the OGG1-Ser326Cys polymorphism and
lymph node metastasis. Our results suggest that the polymorphism of the RAD51, OGG1 and XPD genes may be linked with
breast cancer by the modulation of the cellular response to oxidative stress and these polymorphisms may be considered as markers in
breast cancer along with the genetic or/and environmental indicators of oxidative stress.