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DNA methylation of CYP19A1 due to aromatase inhibitor therapy, the resulting effects on cognitive function in women with postmenopausal breast cancer, and mitigation of cognitive decline with exercise

Zabala Centeno, Julieta (2024) DNA methylation of CYP19A1 due to aromatase inhibitor therapy, the resulting effects on cognitive function in women with postmenopausal breast cancer, and mitigation of cognitive decline with exercise. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Breast cancer in women is well known for changing the day-to-day life of an individual due to many factors. An important factor in the life changing aspects of an individual’s life include the therapies administered to treat breast cancer, for example, aromatase inhibitor therapy (AI). The inhibition of aromatase directly causes a decrease in estrogen production. In theory, while this change aids in decreased tumor growth for women with hormone-receptor positive breast cancer, the positive benefits of estrogen also are paused. For example, estrogen’s neuroprotection benefits are stripped, and neurons are more susceptible to damage from reactive oxygen species and disease processes. Therefore, cognitive function in these individuals has been demonstrated to decrease significantly due to the administration of AI in women with breast cancer, which may influence Quality of Life (QoL). While it is known that AI therapy decreases estrogen, this study researches a more in-depth mechanism, theorizing that DNA Methylation of the gene coding for aromatase, CYP19A1, influences cognitive function in terms of processing speed and that an exercise intervention may mitigate the negative effects of AI therapy and consequent decreased cognitive function.
Participants (n=153) were postmenopausal women with early-stage breast cancer destined to start AI therapy. Cognitive function was measured with a battery of measures including tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Processing speed was evaluated by the Grooved Pegboard Test and Digit Vigilance Test (DVT). DNA Methylation data was collected with the Illumina Infinium EPIC 1.0 and 48 CpG sites within and around CYP19A1 evaluated. The only significant findings were for the association of baseline (pre-AI and pre-randomization to the intervention) DNA methylation and baseline processing speed for a set of CpG sites after adjusting for age, years of education, and verbal intelligence with cg01879211 having the lowest p-value (adj p-value 0.0085). However, these relationships were not significant following correction for multiple testing.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zabala Centeno, Julietajulietazab@hotmail.comjuz48
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorConley,
Committee MemberBender,
Committee MemberMerriman,
Committee MemberHarris,
Date: 24 April 2024
Date Type: Publication
Defense Date: 11 April 2024
Approval Date: 24 April 2024
Submission Date: 19 April 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 28
Institution: University of Pittsburgh
Schools and Programs: David C. Frederick Honors College
School of Nursing > Nursing
Degree: BSN - Bachelor of Science in Nursing
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: CpG sites, CpG, Moderate Aerobic Exercise, Hormone-Recpetive Breast Cancer
Date Deposited: 24 Apr 2024 15:06
Last Modified: 24 Apr 2024 15:06


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