Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Koleck TA

PROVIDER: S-EPMC4826652 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Koleck Theresa A TA Bender Catherine M CM Sereika Susan M SM Brufsky Adam M AM Lembersky Barry C BC McAuliffe Priscilla F PF Puhalla Shannon L SL Rastogi Priya P Conley Yvette P YP

SpringerPlus 20160409

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27099827

Similar Datasets

Project description:PURPOSE:Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance. PATIENTS AND METHODS:The sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles. RESULTS:With the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score. CONCLUSION:Associations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets