Limits...
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 of DNA repair genes in non-muscle-invasive and muscle-invasive tumors depending on their grades. (a) The frequencies of XPD Asp312Asn polymorphisms in Ta/T1 low grade tumors (227 samples) as compared to Ta/T1 high grade neoplasms (59 samples) as well as in T ≥ 2 low grade tumors (24 samples) as opposed to T ≥ 2 high grade neoplasms (97 samples). In the latter case, the frequencies of the Asp/Asp, Asn/Asn, and Asn/Asn+Asp/Asn genotypes and the Asn alleles were as follows: 50% and 28.9% (p = 0.049), 8.3% and 20.6% (p = 0.16), 50% and 71.1% (p = 0.049), and 29.2% and 45.9% (p = 0.036) in T ≥ 2 low grade and T ≥ 2 high grade tumors, respectively. (b) The frequencies of XPD (codon 751) and ERCC6 (codon 399) polymorphisms in T ≥ 2 low grade tumors (24 samples for each polymorphisms) as compared to T ≥ 2 high grade neoplasms (95 and 97 samples, resp.).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4663333&req=5

fig3: Distribution of some genotypes/alleles of DNA repair genes in non-muscle-invasive and muscle-invasive tumors depending on their grades. (a) The frequencies of XPD Asp312Asn polymorphisms in Ta/T1 low grade tumors (227 samples) as compared to Ta/T1 high grade neoplasms (59 samples) as well as in T ≥ 2 low grade tumors (24 samples) as opposed to T ≥ 2 high grade neoplasms (97 samples). In the latter case, the frequencies of the Asp/Asp, Asn/Asn, and Asn/Asn+Asp/Asn genotypes and the Asn alleles were as follows: 50% and 28.9% (p = 0.049), 8.3% and 20.6% (p = 0.16), 50% and 71.1% (p = 0.049), and 29.2% and 45.9% (p = 0.036) in T ≥ 2 low grade and T ≥ 2 high grade tumors, respectively. (b) The frequencies of XPD (codon 751) and ERCC6 (codon 399) polymorphisms in T ≥ 2 low grade tumors (24 samples for each polymorphisms) as compared to T ≥ 2 high grade neoplasms (95 and 97 samples, resp.).

Mentions: When dividing tumors into four categories (Ta/T1 low, Ta/T1 high, T ≥ 2 low, and T ≥ 2 high), evident differences were found only in muscle-invasive carcinomas, with the homozygous wild type genotype of the XPD gene (codon 312) being associated with low grade cancer, whereas the frequencies of genotypes containing a variant Asn allele were significantly increased in high grade neoplasms (Figure 3(a)). Two other polymorphisms (XPD Lys751Gln and ERCC6 Gly399Asp) showed similar trends, but the differences between T ≥ 2 low grade tumors and T ≥ 2 high grade carcinomas were not statistically confirmed (Figure 3(b)).


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 of DNA repair genes in non-muscle-invasive and muscle-invasive tumors depending on their grades. (a) The frequencies of XPD Asp312Asn polymorphisms in Ta/T1 low grade tumors (227 samples) as compared to Ta/T1 high grade neoplasms (59 samples) as well as in T ≥ 2 low grade tumors (24 samples) as opposed to T ≥ 2 high grade neoplasms (97 samples). In the latter case, the frequencies of the Asp/Asp, Asn/Asn, and Asn/Asn+Asp/Asn genotypes and the Asn alleles were as follows: 50% and 28.9% (p = 0.049), 8.3% and 20.6% (p = 0.16), 50% and 71.1% (p = 0.049), and 29.2% and 45.9% (p = 0.036) in T ≥ 2 low grade and T ≥ 2 high grade tumors, respectively. (b) The frequencies of XPD (codon 751) and ERCC6 (codon 399) polymorphisms in T ≥ 2 low grade tumors (24 samples for each polymorphisms) as compared to T ≥ 2 high grade neoplasms (95 and 97 samples, resp.).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Distribution of some genotypes/alleles of DNA repair genes in non-muscle-invasive and muscle-invasive tumors depending on their grades. (a) The frequencies of XPD Asp312Asn polymorphisms in Ta/T1 low grade tumors (227 samples) as compared to Ta/T1 high grade neoplasms (59 samples) as well as in T ≥ 2 low grade tumors (24 samples) as opposed to T ≥ 2 high grade neoplasms (97 samples). In the latter case, the frequencies of the Asp/Asp, Asn/Asn, and Asn/Asn+Asp/Asn genotypes and the Asn alleles were as follows: 50% and 28.9% (p = 0.049), 8.3% and 20.6% (p = 0.16), 50% and 71.1% (p = 0.049), and 29.2% and 45.9% (p = 0.036) in T ≥ 2 low grade and T ≥ 2 high grade tumors, respectively. (b) The frequencies of XPD (codon 751) and ERCC6 (codon 399) polymorphisms in T ≥ 2 low grade tumors (24 samples for each polymorphisms) as compared to T ≥ 2 high grade neoplasms (95 and 97 samples, resp.).
Mentions: When dividing tumors into four categories (Ta/T1 low, Ta/T1 high, T ≥ 2 low, and T ≥ 2 high), evident differences were found only in muscle-invasive carcinomas, with the homozygous wild type genotype of the XPD gene (codon 312) being associated with low grade cancer, whereas the frequencies of genotypes containing a variant Asn allele were significantly increased in high grade neoplasms (Figure 3(a)). Two other polymorphisms (XPD Lys751Gln and ERCC6 Gly399Asp) showed similar trends, but the differences between T ≥ 2 low grade tumors and T ≥ 2 high grade carcinomas were not statistically confirmed (Figure 3(b)).

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