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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 wild type homozygous combinations in non-muscle-invasive and muscle-invasive urothelial carcinomas. 6 hmz correspond to combination of all six wild type homozygotes; 5 hmz correspond to total combinations containing any five wild type homozygotes. The Ta/T1 group was represented by 289 samples, whereas the T ≥ 2 group consisted of 120 samples.
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fig4: Distribution of wild type homozygous combinations in non-muscle-invasive and muscle-invasive urothelial carcinomas. 6 hmz correspond to combination of all six wild type homozygotes; 5 hmz correspond to total combinations containing any five wild type homozygotes. The Ta/T1 group was represented by 289 samples, whereas the T ≥ 2 group consisted of 120 samples.

Mentions: Based on the assumption that the wild type of DNA excision repair genes may provide elimination of mutagenic/carcinogenic DNA lesions thus promoting both decrease in cancer risk and inhibition of tumor expansion/malignancy, the frequencies of combined homozygous wild type alleles were estimated depending on T stages. The combination involving Ser/Ser, Arg/Arg, Asp/Asp, Lys/Lys, Met/Met, and Gly/Gly genotypes of OGG1 (codon 326), XRCC1 (codon 399), XPD (codons 312 and 751), and ERCC6 (codons 1097 and 399), respectively, was a rare event occurring only in Ta/T1 tumors (2.1%). As shown in Figure 4(a), the total frequency of combinations represented by any five homozygous wild type genotypes was significantly higher in non-muscle-invasive carcinomas (18.7%) as compared to advanced tumors (7.9%) and together with the former combination containing all six wild type homozygotes they achieved 20.8% in Ta/T1 neoplasms as opposed to 7.9% in T ≥ 2 tumors (Figure 4(b)). Accordingly, homozygosity for the wild type alleles of the DNA repair genes under study seemed to prevent tumor expansion. The distribution of these combinations did not depend on tumor grades.


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 wild type homozygous combinations in non-muscle-invasive and muscle-invasive urothelial carcinomas. 6 hmz correspond to combination of all six wild type homozygotes; 5 hmz correspond to total combinations containing any five wild type homozygotes. The Ta/T1 group was represented by 289 samples, whereas the T ≥ 2 group consisted of 120 samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Distribution of wild type homozygous combinations in non-muscle-invasive and muscle-invasive urothelial carcinomas. 6 hmz correspond to combination of all six wild type homozygotes; 5 hmz correspond to total combinations containing any five wild type homozygotes. The Ta/T1 group was represented by 289 samples, whereas the T ≥ 2 group consisted of 120 samples.
Mentions: Based on the assumption that the wild type of DNA excision repair genes may provide elimination of mutagenic/carcinogenic DNA lesions thus promoting both decrease in cancer risk and inhibition of tumor expansion/malignancy, the frequencies of combined homozygous wild type alleles were estimated depending on T stages. The combination involving Ser/Ser, Arg/Arg, Asp/Asp, Lys/Lys, Met/Met, and Gly/Gly genotypes of OGG1 (codon 326), XRCC1 (codon 399), XPD (codons 312 and 751), and ERCC6 (codons 1097 and 399), respectively, was a rare event occurring only in Ta/T1 tumors (2.1%). As shown in Figure 4(a), the total frequency of combinations represented by any five homozygous wild type genotypes was significantly higher in non-muscle-invasive carcinomas (18.7%) as compared to advanced tumors (7.9%) and together with the former combination containing all six wild type homozygotes they achieved 20.8% in Ta/T1 neoplasms as opposed to 7.9% in T ≥ 2 tumors (Figure 4(b)). Accordingly, homozygosity for the wild type alleles of the DNA repair genes under study seemed to prevent tumor expansion. The distribution of these combinations did not depend on tumor grades.

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