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Multi-Omics of Breast Cancer Related-Fatigue and its Mitigation by Exercise

Davis, Tara Sinead (2023) Multi-Omics of Breast Cancer Related-Fatigue and its Mitigation by Exercise. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Cancer-related fatigue (CRF) remains the most common symptom experienced in postmenopausal woman diagnosed with breast cancer. Based on preliminary work it likely that oxidative stress related biological mechanisms may influence CRF outcomes (i.e., severity, occurrence, and clinically relevant change overtime). In addition to biological factors social factors have also been shown to be important to the variability of CRF outcomes. The purpose of this dissertation study was to explore genomic and social factors that may explain variability of CRF outcomes in postmenopausal women with early-stage hormone receptor breast cancer in the context of an exercise intervention. Aim 1 explored genomic and social factors that explain variability in pretreatment CRF outcomes. In Aim 2 genomic and social factors were explored to explain the variability that cancer therapy had on CRF outcomes. Lastly, Aim 3 explored genomic and social factors that explain variation in response to an exercise intervention to mitigate CRF and identify genes influenced by the exercise intervention. In a sample of 116 women which consisted of n = 56 in the usual care group (received cancer therapy) and n = 60 in the exercise group (received cancer therapy and an exercise intervention) CRF outcomes were evaluated. Genotype data was generated for 16 functional SNPs related to 7 biologically plausible breast cancer-related candidate genes (CAT, KEAP1, NFE2L2, PRDX1, SOD1, SOD2, and TXN) identified in Ingenuity Pathway Analysis software and in the literature. Regression models were used to evaluate CRF severity (linear regression), occurrence (logistic regression) and clinically relevant change (logistic regression) for each omic and social factor. Covariates were identified using a data-driven and a priori method, and included VO2 max, body mass index (BMI), age, depression, anxiety, pain, and sleep deprivation. False discovery rate (FDR) corrections were used to adjust for multiple testing. Increased methylation at CpG site cg02881230 located in the PRDX1 gene was associated with increased CRF severity at time point 2 in the exercise group (beta = 21.7231, p = 0.0003, 95% CI = 10.97 to 32.47, FDR corrected p = 0.0368). Overall, results from this exploratory study suggest the importance of PRDX1 to CRF response in the context of an exercise intervention.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Davis, Tara Sineadtsd21@pitt.edutsd210000-0002-6293-3602
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley,
Committee MemberBender,
Committee MemberMiaskowski,
Committee MemberRosenzweig,
Committee MemberKoleck,
Date: 11 August 2023
Date Type: Publication
Defense Date: 25 July 2023
Approval Date: 11 August 2023
Submission Date: 10 August 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 199
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Postmenopausal Breast Cancer, Oxidative Stress, Exercise, Single Nucleotide Polymorphism, DNA Methylation,
Date Deposited: 11 Aug 2023 19:14
Last Modified: 11 Aug 2023 19:14


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