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Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study

PURPOSE: The purpose of this exploratory candidate gene association study was to examine relationships between polymorphisms in oxidative stress and DNA repair genes and pre-adjuvant therapy cognitive function (CF) in postmenopausal women diagnosed with early stage-breast cancer. METHODS: Using a ne...

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Autores principales: Koleck, Theresa A., Bender, Catherine M., Sereika, Susan M., Brufsky, Adam M., Lembersky, Barry C., McAuliffe, Priscilla F., Puhalla, Shannon L., Rastogi, Priya, Conley, Yvette P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826652/
https://www.ncbi.nlm.nih.gov/pubmed/27099827
http://dx.doi.org/10.1186/s40064-016-2061-4
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author Koleck, Theresa A.
Bender, Catherine M.
Sereika, Susan M.
Brufsky, Adam M.
Lembersky, Barry C.
McAuliffe, Priscilla F.
Puhalla, Shannon L.
Rastogi, Priya
Conley, Yvette P.
author_facet Koleck, Theresa A.
Bender, Catherine M.
Sereika, Susan M.
Brufsky, Adam M.
Lembersky, Barry C.
McAuliffe, Priscilla F.
Puhalla, Shannon L.
Rastogi, Priya
Conley, Yvette P.
author_sort Koleck, Theresa A.
collection PubMed
description PURPOSE: The purpose of this exploratory candidate gene association study was to examine relationships between polymorphisms in oxidative stress and DNA repair genes and pre-adjuvant therapy cognitive function (CF) in postmenopausal women diagnosed with early stage-breast cancer. METHODS: Using a neuropsychological test battery, CF was assessed in 138 women diagnosed with breast cancer prior to initiation of adjuvant therapy and 81 age- and education-matched controls and summarized across eight composites. Participants were genotyped for 39 functional or tagging single nucleotide polymorphisms (SNPs) of select oxidative stress (CAT, GPX1, SEPP1, SOD1, and SOD2) and DNA repair (ERCC2, ERCC3, ERCC5, and PARP1) genes. Multiple linear regression was used to determine if the presence or absence of one or more minor alleles account for variability in CF composite scores. Based on regression findings from the analysis of individual SNPs, weighted multi-gene, multi-polymorphism genetic risk scores (GRSs) were calculated to evaluate the collective effect of possession of multiple protective and/or risk alleles. RESULTS: Each CF composite was significantly (p < 0.05) associated with one or more oxidative stress and DNA repair gene polymorphisms evaluated either by SNP main effects and/or SNP-by-prescribed breast cancer treatment group interactions. Each computed GRS was found to be significantly (p < 0.001) related to its corresponding CF composite. All associations were positive suggesting that as overall genetic protection increases, CF composite score increases (indicating better performance). CONCLUSIONS: These findings suggest that genetic variation in the oxidative stress and DNA repair pathways may play an important role in pre-adjuvant therapy CF in breast cancer survivors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2061-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-48266522016-04-20 Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study Koleck, Theresa A. Bender, Catherine M. Sereika, Susan M. Brufsky, Adam M. Lembersky, Barry C. McAuliffe, Priscilla F. Puhalla, Shannon L. Rastogi, Priya Conley, Yvette P. Springerplus Research PURPOSE: The purpose of this exploratory candidate gene association study was to examine relationships between polymorphisms in oxidative stress and DNA repair genes and pre-adjuvant therapy cognitive function (CF) in postmenopausal women diagnosed with early stage-breast cancer. METHODS: Using a neuropsychological test battery, CF was assessed in 138 women diagnosed with breast cancer prior to initiation of adjuvant therapy and 81 age- and education-matched controls and summarized across eight composites. Participants were genotyped for 39 functional or tagging single nucleotide polymorphisms (SNPs) of select oxidative stress (CAT, GPX1, SEPP1, SOD1, and SOD2) and DNA repair (ERCC2, ERCC3, ERCC5, and PARP1) genes. Multiple linear regression was used to determine if the presence or absence of one or more minor alleles account for variability in CF composite scores. Based on regression findings from the analysis of individual SNPs, weighted multi-gene, multi-polymorphism genetic risk scores (GRSs) were calculated to evaluate the collective effect of possession of multiple protective and/or risk alleles. RESULTS: Each CF composite was significantly (p < 0.05) associated with one or more oxidative stress and DNA repair gene polymorphisms evaluated either by SNP main effects and/or SNP-by-prescribed breast cancer treatment group interactions. Each computed GRS was found to be significantly (p < 0.001) related to its corresponding CF composite. All associations were positive suggesting that as overall genetic protection increases, CF composite score increases (indicating better performance). CONCLUSIONS: These findings suggest that genetic variation in the oxidative stress and DNA repair pathways may play an important role in pre-adjuvant therapy CF in breast cancer survivors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2061-4) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-04-09 /pmc/articles/PMC4826652/ /pubmed/27099827 http://dx.doi.org/10.1186/s40064-016-2061-4 Text en © Koleck et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Koleck, Theresa A.
Bender, Catherine M.
Sereika, Susan M.
Brufsky, Adam M.
Lembersky, Barry C.
McAuliffe, Priscilla F.
Puhalla, Shannon L.
Rastogi, Priya
Conley, Yvette P.
Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title_full Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title_fullStr Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title_full_unstemmed Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title_short Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
title_sort polymorphisms in dna repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826652/
https://www.ncbi.nlm.nih.gov/pubmed/27099827
http://dx.doi.org/10.1186/s40064-016-2061-4
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