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Cognitive Function and Breast Cancer: Genomics and Disease Characteristics

Koleck, Theresa A. (2016) Cognitive Function and Breast Cancer: Genomics and Disease Characteristics. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Cognitive dysfunction is one of the most common and burdensome symptoms experienced by breast cancer survivors. This exploratory, ancillary study investigated the hypothesis that heterogeneity in the biology of breast cancers, including differences in clinicopathologic tumor
features (CTFs) and host DNA variation in genes used clinically for breast cancer prognostication, may account for a proportion of variability in pretreatment (i.e., prior to initiation of systemic adjuvant therapy) cognitive performance among postmenopausal women diagnosed with early-stage breast cancer. The parent study, Cognitive Impairment Related to Anastrozole Use in Women, provided pretreatment cognitive function data, CTF information from surgical pathology reports of women with breast cancer prescribed to initiate anastrozole±chemotherapy (n=329) at a future time, and biospecimens for the women with breast cancer (n=138) and age- and education-matched healthy controls (n=82), who were identically assessed for cognitive function. We genotyped 131 single nucleotide polymorphisms (SNPs) representing 25 breast cancer-associated 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). Genetic risk/protection scores (GRSs) were calculated for each cognitive function composite to evaluate the collective effect of possession of multiple SNPs on cognitive performance. Multiple linear regression modeling was used to determine if CTFs, SNPs, and/or interactions between CTFs and GRSs accounted for variability in cognitive performance. We found that CTFs related to cancer stage, tumor size, tumor focality, tumor location, histologic type and grade, hormone receptor and HER2 expression, cellular proliferation, as well as Oncotype DX® Breast Cancer Assay Recurrence Score® and Magee Equation recurrence score were individually significantly (p<0.05) associated with performance for one or more cognitive function composites. With the exception of CMC2, MMP11, and RACGAP1, significant (p<0.05) SNP main effect and/or SNP-by-prescribed treatment group interactions were observed individually between at least one cognitive function composite and one or more SNPs. Each GRS was significantly (p<0.001) associated with its respective cognitive function composite score. The findings from this dissertation study lay the foundation for a line of research to identify pathophysiologic mechanisms of and clinically relevant biomarkers for breast cancer-related cognitive dysfunction.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Koleck, Theresa A.tat30@pitt.eduTAT30
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley, Yvette P.yconley@pitt.eduYCONLEY
Committee MemberBender, Catherine M.cbe100@pitt.eduCBE100
Committee MemberSereika, Susan M.ssereika@pitt.eduSSEREIKA
Committee MemberRyan, Christopher M.christopher.ryan@ucsf.eduCMR14
Committee MemberClark, Beth Z.clarkbz@upmc.eduCLARKB
Date: 28 April 2016
Date Type: Publication
Defense Date: 11 April 2016
Approval Date: 28 April 2016
Submission Date: 25 April 2016
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 267
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: breast neoplasms, cognition, genetics, pathology, biomarkers
Date Deposited: 28 Apr 2016 18:58
Last Modified: 28 Apr 2017 05:15


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