BER gene polymorphisms associated with key molecular events in bladder cancer

Summary. Aim: Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed...

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Дата:2018
Автори: Smal, M.P., Kuzhir, T.D., Savina, N.V., Nikitchenko, N.V., Rolevich, A.I., Krasny, S.A., Goncharova, R.I.
Формат: Стаття
Мова:English
Опубліковано: PH Akademperiodyka 2018
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Онлайн доступ:https://exp-oncology.com.ua/index.php/Exp/article/view/2018-4-5
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Назва журналу:Experimental Oncology

Репозитарії

Experimental Oncology
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institution Experimental Oncology
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datestamp_date 2025-04-30T11:55:13Z
collection OJS
language English
topic BER gene polymorphisms
bladder cancer
LOH
methylation
mutability
spellingShingle BER gene polymorphisms
bladder cancer
LOH
methylation
mutability
Smal, M.P.
Kuzhir, T.D.
Savina, N.V.
Nikitchenko, N.V.
Rolevich, A.I.
Krasny, S.A.
Goncharova, R.I.
BER gene polymorphisms associated with key molecular events in bladder cancer
topic_facet BER gene polymorphisms
bladder cancer
LOH
methylation
mutability
BER gene polymorphisms
bladder cancer
LOH
methylation
mutability
format Article
author Smal, M.P.
Kuzhir, T.D.
Savina, N.V.
Nikitchenko, N.V.
Rolevich, A.I.
Krasny, S.A.
Goncharova, R.I.
author_facet Smal, M.P.
Kuzhir, T.D.
Savina, N.V.
Nikitchenko, N.V.
Rolevich, A.I.
Krasny, S.A.
Goncharova, R.I.
author_sort Smal, M.P.
title BER gene polymorphisms associated with key molecular events in bladder cancer
title_short BER gene polymorphisms associated with key molecular events in bladder cancer
title_full BER gene polymorphisms associated with key molecular events in bladder cancer
title_fullStr BER gene polymorphisms associated with key molecular events in bladder cancer
title_full_unstemmed BER gene polymorphisms associated with key molecular events in bladder cancer
title_sort ber gene polymorphisms associated with key molecular events in bladder cancer
title_alt BER gene polymorphisms associated with key molecular events in bladder cancer
description Summary. Aim: Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed to include interplay between BER gene polymorphisms and key mutational, epigenetic and chromosomal events in tumor tissues. The present study was aimed at elucidating potential gene-gene interaction and assessing their mutual effects in bladder cancer (BC). Materials and Methods: The earlier obtained data on genotyping patients with verified diagnosis of BC for OGG1 rs1052133 (Ser326Cys) and XRCC1 rs25487 (Arg399Gln) polymorphisms were used for this study. The tumor tissue samples from the same patients were analyzed for mutations, epigenetic variations and losses of heterozygosity in some key genes involved in divergent pathogenic pathways of BC. Results: It was shown that the OGG1 (326 codon) heterozygous genotype as well as the minor 326Cys allele can intensify a mutational response of the RAS locus in urothelial carcinomas in the total cohort of patients simultaneously decreasing the mutation rates in the PIK3CA locus in smokers. The XRCC1 (399 codon) heterozygous genotype as well as the minor 399Gln allele reduced the frequency of LOH in the PTEN and TNKS genes, but did not affect the mutational variability in any locus tested. Both polymorphisms influenced the methylation status, carriers of OGG1 326Ser/Cys or Ser/Cys+Cys/Cys genotypes demonstrating increased frequency of methylated RUNX3 and ISL1 genes whereas the similar effect of XRCC1 polymorphism concerning methylation of p16 and TIMP3 genes. When dividing the total cohort into groups based on the extent of tumor spread, the observed associations were characteristic of non-muscle invasive BC. Conclusion: The BER gene polymorphisms contributed to modification of key molecular events in urothelial carcinomas. Their mutual effects mainly manifested in non-muscle invasive BC. The underlying mechanisms as well as possible clinical outcomes need to be further explored to propose novel prognostic biomarkers for BC.
publisher PH Akademperiodyka
publishDate 2018
url https://exp-oncology.com.ua/index.php/Exp/article/view/2018-4-5
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spelling oai:ojs2.ex.aqua-time.com.ua:article-2832025-04-30T11:55:13Z BER gene polymorphisms associated with key molecular events in bladder cancer BER gene polymorphisms associated with key molecular events in bladder cancer Smal, M.P. Kuzhir, T.D. Savina, N.V. Nikitchenko, N.V. Rolevich, A.I. Krasny, S.A. Goncharova, R.I. BER gene polymorphisms, bladder cancer, LOH, methylation, mutability BER gene polymorphisms, bladder cancer, LOH, methylation, mutability Summary. Aim: Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed to include interplay between BER gene polymorphisms and key mutational, epigenetic and chromosomal events in tumor tissues. The present study was aimed at elucidating potential gene-gene interaction and assessing their mutual effects in bladder cancer (BC). Materials and Methods: The earlier obtained data on genotyping patients with verified diagnosis of BC for OGG1 rs1052133 (Ser326Cys) and XRCC1 rs25487 (Arg399Gln) polymorphisms were used for this study. The tumor tissue samples from the same patients were analyzed for mutations, epigenetic variations and losses of heterozygosity in some key genes involved in divergent pathogenic pathways of BC. Results: It was shown that the OGG1 (326 codon) heterozygous genotype as well as the minor 326Cys allele can intensify a mutational response of the RAS locus in urothelial carcinomas in the total cohort of patients simultaneously decreasing the mutation rates in the PIK3CA locus in smokers. The XRCC1 (399 codon) heterozygous genotype as well as the minor 399Gln allele reduced the frequency of LOH in the PTEN and TNKS genes, but did not affect the mutational variability in any locus tested. Both polymorphisms influenced the methylation status, carriers of OGG1 326Ser/Cys or Ser/Cys+Cys/Cys genotypes demonstrating increased frequency of methylated RUNX3 and ISL1 genes whereas the similar effect of XRCC1 polymorphism concerning methylation of p16 and TIMP3 genes. When dividing the total cohort into groups based on the extent of tumor spread, the observed associations were characteristic of non-muscle invasive BC. Conclusion: The BER gene polymorphisms contributed to modification of key molecular events in urothelial carcinomas. Their mutual effects mainly manifested in non-muscle invasive BC. The underlying mechanisms as well as possible clinical outcomes need to be further explored to propose novel prognostic biomarkers for BC. Summary. Aim: Base excision repair (BER) gene polymorphisms are known to play an independent role in predisposition to developing different cancers as well as to be associated with clinicopathological traits of the disease modifying its clinical outcomes. One of the underlying mechanisms is presumed to include interplay between BER gene polymorphisms and key mutational, epigenetic and chromosomal events in tumor tissues. The present study was aimed at elucidating potential gene-gene interaction and assessing their mutual effects in bladder cancer (BC). Materials and Methods: The earlier obtained data on genotyping patients with verified diagnosis of BC for OGG1 rs1052133 (Ser326Cys) and XRCC1 rs25487 (Arg399Gln) polymorphisms were used for this study. The tumor tissue samples from the same patients were analyzed for mutations, epigenetic variations and losses of heterozygosity in some key genes involved in divergent pathogenic pathways of BC. Results: It was shown that the OGG1 (326 codon) heterozygous genotype as well as the minor 326Cys allele can intensify a mutational response of the RAS locus in urothelial carcinomas in the total cohort of patients simultaneously decreasing the mutation rates in the PIK3CA locus in smokers. The XRCC1 (399 codon) heterozygous genotype as well as the minor 399Gln allele reduced the frequency of LOH in the PTEN and TNKS genes, but did not affect the mutational variability in any locus tested. Both polymorphisms influenced the methylation status, carriers of OGG1 326Ser/Cys or Ser/Cys+Cys/Cys genotypes demonstrating increased frequency of methylated RUNX3 and ISL1 genes whereas the similar effect of XRCC1 polymorphism concerning methylation of p16 and TIMP3 genes. When dividing the total cohort into groups based on the extent of tumor spread, the observed associations were characteristic of non-muscle invasive BC. Conclusion: The BER gene polymorphisms contributed to modification of key molecular events in urothelial carcinomas. Their mutual effects mainly manifested in non-muscle invasive BC. The underlying mechanisms as well as possible clinical outcomes need to be further explored to propose novel prognostic biomarkers for BC. PH Akademperiodyka 2018-12-22 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/2018-4-5 Experimental Oncology; Vol. 40 No. 4 (2018): Experimental Oncology; 288-298 Експериментальна онкологія; Том 40 № 4 (2018): Експериментальна онкологія; 288-298 2312-8852 1812-9269 en https://exp-oncology.com.ua/index.php/Exp/article/view/2018-4-5/2018-4-5 Copyright (c) 2023 Experimental Oncology https://creativecommons.org/licenses/by-nc/4.0/