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The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer.

Savina NV, Nikitchenko NV, Kuzhir TD, Rolevich AI, Krasny SA, Goncharova RI - Oxid Med Cell Longev (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.

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.

No MeSH data available.


Related in: MedlinePlus

Distribution of some genotypes/alleles in patients with papillary urothelial neoplasms of low malignant potential (LMP, 11 samples) as compared to high grade carcinomas (high, 156 samples). Four coupled bars correspond to ERCC6 Met1097Val polymorphisms. The frequencies of the Met/Met genotype are 81.8% and 49.4% in LMN and high grade tumors, whereas the frequencies of the Met/Val + Val/Val genotypes are 18.2% and 50.6% in the same types of urothelial carcinomas, respectively. The last coupled bars reflect the frequencies of the OGG1 (codon 326) heterozygous genotype, which are 54.5% in LMP neoplasms and 26.3% in high grade tumors.
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fig2: Distribution of some genotypes/alleles in patients with papillary urothelial neoplasms of low malignant potential (LMP, 11 samples) as compared to high grade carcinomas (high, 156 samples). Four coupled bars correspond to ERCC6 Met1097Val polymorphisms. The frequencies of the Met/Met genotype are 81.8% and 49.4% in LMN and high grade tumors, whereas the frequencies of the Met/Val + Val/Val genotypes are 18.2% and 50.6% in the same types of urothelial carcinomas, respectively. The last coupled bars reflect the frequencies of the OGG1 (codon 326) heterozygous genotype, which are 54.5% in LMP neoplasms and 26.3% in high grade tumors.

Mentions: The distribution of genotypes/alleles for polymorphisms of DNA repair genes did not depend on tumor grades. However, the analysis of genetic variations in papillary neoplasms of low malignant potential (PNLMP) as compared with high grade or poorly differentiated cancer revealed some peculiarities concerning ERCC6 Met1097Val and OGG1 Ser326Cys polymorphisms (Figure 2). The frequencies of homozygous wild type genotype of ERCC6 gene and heterozygous genotype of the OGG1 gene were significantly increased in LMP tumors, whereas the genotypes containing at least one variant allele of the ERCC6 gene occurred more often in patients with G3 or high grade urothelial carcinomas. Thus, neoplasms of low malignant potential were distinct from others with respect to genotype distribution of both the OGG1 Ser326Cys and the ERCC6 Met1097Val polymorphisms.


The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer.

Savina NV, Nikitchenko NV, Kuzhir TD, Rolevich AI, Krasny SA, Goncharova RI - Oxid Med Cell Longev (2015)

Distribution of some genotypes/alleles in patients with papillary urothelial neoplasms of low malignant potential (LMP, 11 samples) as compared to high grade carcinomas (high, 156 samples). Four coupled bars correspond to ERCC6 Met1097Val polymorphisms. The frequencies of the Met/Met genotype are 81.8% and 49.4% in LMN and high grade tumors, whereas the frequencies of the Met/Val + Val/Val genotypes are 18.2% and 50.6% in the same types of urothelial carcinomas, respectively. The last coupled bars reflect the frequencies of the OGG1 (codon 326) heterozygous genotype, which are 54.5% in LMP neoplasms and 26.3% in high grade tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663333&req=5

fig2: Distribution of some genotypes/alleles in patients with papillary urothelial neoplasms of low malignant potential (LMP, 11 samples) as compared to high grade carcinomas (high, 156 samples). Four coupled bars correspond to ERCC6 Met1097Val polymorphisms. The frequencies of the Met/Met genotype are 81.8% and 49.4% in LMN and high grade tumors, whereas the frequencies of the Met/Val + Val/Val genotypes are 18.2% and 50.6% in the same types of urothelial carcinomas, respectively. The last coupled bars reflect the frequencies of the OGG1 (codon 326) heterozygous genotype, which are 54.5% in LMP neoplasms and 26.3% in high grade tumors.
Mentions: The distribution of genotypes/alleles for polymorphisms of DNA repair genes did not depend on tumor grades. However, the analysis of genetic variations in papillary neoplasms of low malignant potential (PNLMP) as compared with high grade or poorly differentiated cancer revealed some peculiarities concerning ERCC6 Met1097Val and OGG1 Ser326Cys polymorphisms (Figure 2). The frequencies of homozygous wild type genotype of ERCC6 gene and heterozygous genotype of the OGG1 gene were significantly increased in LMP tumors, whereas the genotypes containing at least one variant allele of the ERCC6 gene occurred more often in patients with G3 or high grade urothelial carcinomas. Thus, neoplasms of low malignant potential were distinct from others with respect to genotype distribution of both the OGG1 Ser326Cys and the ERCC6 Met1097Val polymorphisms.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.

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.

No MeSH data available.


Related in: MedlinePlus