Abstract for presentation at 11th International Congress of Human Genetics

DNA damage and repair in gastric cancer: a correlation with the OGG1 and RAD51 genes polymorphisms

  • Janusz Blasiak, Department of Molecular Genetics, University of Lodz, Poland
  • Tomasz Poplawski, Department of Molecular Genetics, University of Lodz, Poland
  • Michal Arabski, Department of Molecular Genetics, University of Lodz, Poland
  • Dorota Kozirowska, Department of Molecular Genetics, University of Lodz, Poland
  • Grazyna Klupinska, Department of Gastroenterology and Internal Medicine, Medical University of Lodz, Poland
  • Zbigniew Morawiec, N. Copernicus Hospital, Poland
  • Maria Morawiec, N. Copernicus Hospital, Poland
  • Jan Chojnacki, Department of Gastroenterology and Internal Medicine, Medical University of Lodz, Poland

    • The cell’s susceptibility to mutagens and its ability to repair DNA lesions are important for induction and development of cancer and they may be affected by variability in many genes, including DNA repair genes. The OGG1 gene encodes glycosylase of base excision repair and Rad51 codes for a key protein in homologues recombination repair. Both can be involved in the repair of oxidative DNA lesion, which can contribute to stomach cancer. In the present work we determined the level of basal and oxidative DNA damage and kinetics of removal of DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes of 30 gastric cancer patients and 30 healthy individuals. The metrics from DNA damage and repair study were correlated with the genotypes of common polymorphisms of the OGG1 and Rad51 genes: a G to C transwersion at 1245 position (exon 7) of the OGG1 gene producing an Ser to Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G to C substitution at position 135 of the RAD51 gene (the G135C polymorphism). The level of DNA damage and the kinetics of DNA repair were evaluated by the alkaline comet assay and oxidative DNA damage was assayed with the use of DNA repair enzymes: endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), recognizing oxidized DNA bases. The genotypes of the polymorphism were determined by restriction fragment length polymorphism PCR. We observed a strong association between gastric cancer occurrence, impaired DNA repair and the G135C polymorphism of the Rad51 gene polymorphism. Moreover, there was a strong correlation between C/G genotype of the G135C polymorphism and stomach cancer occurrence in subjects with high level of oxidatively damaged DNA. We did not observe any correlation between the Ser1245Cys polymorphism of the OGG1 gene and gastric cancer, including subjects with impaired DNA repair or high levels of endogenous oxidative DNA lesions. Therefore, our result suggest that the G135C polymorphism of the Rad51 gene may be linked with gastric cancer by the modulation of the cellular response to oxidative stress.
    This work was supported by the Polish Committee of Scientific Research (KBN), grant no. 2 P05D 068 27

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