Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study.
OBJECTIVE
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.
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261 USA.
Theresa A
TA
Koleck
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261 USA.
Catherine M
CM
Bender
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261 USA ; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261 USA ; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261 USA.
Susan M
SM
Sereika
Division of Hematology/Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 300 Halket Street, Pittsburgh, PA 15213 USA ; University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232 USA ; School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261 USA.
Adam M
AM
Brufsky
Division of Hematology/Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 300 Halket Street, Pittsburgh, PA 15213 USA ; University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232 USA.
Barry C
BC
Lembersky
University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232 USA ; School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261 USA ; Division of Breast Surgical Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 300 Halket Street, Pittsburgh, PA 15213 USA.
Priscilla F
PF
McAuliffe
Division of Hematology/Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 300 Halket Street, Pittsburgh, PA 15213 USA ; School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261 USA.
Shannon L
SL
Puhalla
Division of Hematology/Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 300 Halket Street, Pittsburgh, PA 15213 USA ; School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261 USA.
Priya
P
Rastogi
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261 USA ; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261 USA.
Yvette P
YP
Conley
Breast neoplasms; Cognition; DNA repair; Genetics; Oxidative stress; Polymorphisms