title: The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer.
abstract: Genome instability and impaired DNA repair are hallmarks of carcinogenesis. The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations. Polymorphism in DNA repair genes involved in nucleotide excision repair (NER) and base excision repair (BER) was studied using the PCR-RFLP method in the Belarusian population to elucidate the possible association of their variations with both bladder cancer risk and clinicopathological features of tumors. The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study. Heterozygosity in the XPD gene (codon 751) increased cancer risk: OR (95% CI) = 1.36 (1.03-1.81), p = 0.031. The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors. Combinations of homozygous wild type alleles occurred with the increased frequency in patients with non-muscle-invasive tumors suggesting that the maintenance of normal DNA repair activity may prevent cancer progression.
authors.affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.
authors.forename: Nataliya V
authors.initials: NV
authors.lastname: Savina
authors.affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.
authors.forename: Nataliya V
authors.initials: NV
authors.lastname: Nikitchenko
authors.affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Kuzhir
authors.affiliation: N.N. Alexandrov National Cancer Centre of Belarus, Lesnoy, 223040 Minsk, Belarus.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Rolevich
authors.affiliation: N.N. Alexandrov National Cancer Centre of Belarus, Lesnoy, 223040 Minsk, Belarus.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Krasny
authors.affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.
authors.forename: Roza I
authors.initials: RI
authors.lastname: Goncharova
mesh_terms: D000328:Adult; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D000075223:Poly-ADP-Ribose Binding Proteins; D012150:Polymorphism, Restriction Fragment Length; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes