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Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study

Deleterious and missense mutations of RAD51C have recently been suggested to modulate the individual susceptibility to hereditary breast and ovarian cancer and unselected ovarian cancer, but not unselected breast cancer (BrC). We enrolled 132 unselected BrC females and 189 cancer-free female subject...

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Autores principales: Gresner, Peter, Gromadzinska, Jolanta, Jablonska, Ewa, Stepnik, Maciej, Zambrano Quispe, Oscar, Twardowska, Ewa, Wasowicz, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208807/
https://www.ncbi.nlm.nih.gov/pubmed/25343521
http://dx.doi.org/10.1371/journal.pone.0110696
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author Gresner, Peter
Gromadzinska, Jolanta
Jablonska, Ewa
Stepnik, Maciej
Zambrano Quispe, Oscar
Twardowska, Ewa
Wasowicz, Wojciech
author_facet Gresner, Peter
Gromadzinska, Jolanta
Jablonska, Ewa
Stepnik, Maciej
Zambrano Quispe, Oscar
Twardowska, Ewa
Wasowicz, Wojciech
author_sort Gresner, Peter
collection PubMed
description Deleterious and missense mutations of RAD51C have recently been suggested to modulate the individual susceptibility to hereditary breast and ovarian cancer and unselected ovarian cancer, but not unselected breast cancer (BrC). We enrolled 132 unselected BrC females and 189 cancer-free female subjects to investigate whether common single nucleotide polymorphisms (SNPs) in non-coding regions of RAD51C modulate the risk of BrC, and whether they affect the level of oxidative stress and the extent/characteristics of DNA damage. Neither SNPs nor reconstructed haplotypes were found to significantly affect the unselected BrC risk. Contrary to this, carriers of rs12946522, rs16943176, rs12946397 and rs17222691 rare-alleles were found to present significantly increased level of blood plasma TBARS compared to respective wild-type homozygotes (p<0.05). Furthermore, these carriers showed significantly decreased fraction of oxidatively generated DNA damage (34% of total damaged DNA) in favor of DNA strand breakage, with no effect on total DNA damage, unlike respective wild-types, among which more evenly distributed proportions between oxidatively damaged DNA (48% of total DNA damage) and DNA strand breakage was found (p<0.0005 for the difference). Such effects were found among both the BrC cases and healthy subjects, indicating that they cannot be assumed as causal factors contributing to BrC development.
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spelling pubmed-42088072014-10-27 Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study Gresner, Peter Gromadzinska, Jolanta Jablonska, Ewa Stepnik, Maciej Zambrano Quispe, Oscar Twardowska, Ewa Wasowicz, Wojciech PLoS One Research Article Deleterious and missense mutations of RAD51C have recently been suggested to modulate the individual susceptibility to hereditary breast and ovarian cancer and unselected ovarian cancer, but not unselected breast cancer (BrC). We enrolled 132 unselected BrC females and 189 cancer-free female subjects to investigate whether common single nucleotide polymorphisms (SNPs) in non-coding regions of RAD51C modulate the risk of BrC, and whether they affect the level of oxidative stress and the extent/characteristics of DNA damage. Neither SNPs nor reconstructed haplotypes were found to significantly affect the unselected BrC risk. Contrary to this, carriers of rs12946522, rs16943176, rs12946397 and rs17222691 rare-alleles were found to present significantly increased level of blood plasma TBARS compared to respective wild-type homozygotes (p<0.05). Furthermore, these carriers showed significantly decreased fraction of oxidatively generated DNA damage (34% of total damaged DNA) in favor of DNA strand breakage, with no effect on total DNA damage, unlike respective wild-types, among which more evenly distributed proportions between oxidatively damaged DNA (48% of total DNA damage) and DNA strand breakage was found (p<0.0005 for the difference). Such effects were found among both the BrC cases and healthy subjects, indicating that they cannot be assumed as causal factors contributing to BrC development. Public Library of Science 2014-10-24 /pmc/articles/PMC4208807/ /pubmed/25343521 http://dx.doi.org/10.1371/journal.pone.0110696 Text en © 2014 Gresner et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gresner, Peter
Gromadzinska, Jolanta
Jablonska, Ewa
Stepnik, Maciej
Zambrano Quispe, Oscar
Twardowska, Ewa
Wasowicz, Wojciech
Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title_full Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title_fullStr Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title_full_unstemmed Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title_short Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics: A Case-Control Study
title_sort single nucleotide polymorphisms in noncoding regions of rad51c do not change the risk of unselected breast cancer but they modulate the level of oxidative stress and the dna damage characteristics: a case-control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208807/
https://www.ncbi.nlm.nih.gov/pubmed/25343521
http://dx.doi.org/10.1371/journal.pone.0110696
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