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The relationship of brain derived neurotrophic factor gene methylation and the pain phenotype in women undergoing aromatase inhibitor therapy for breast cancer treatment

Levy, Sarah D. (2024) The relationship of brain derived neurotrophic factor gene methylation and the pain phenotype in women undergoing aromatase inhibitor therapy for breast cancer treatment. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Introduction: The oncologic community’s understanding of pain and cancer treatment is far from reaching definitive answers and correlations that can allow advancements in these treatments and adjuvant therapies. This study’s purpose is to investigate genetic variation and methylation of the BDNF gene and associated pain with Aromatase Inhibitor (AI) therapy treatment for breast cancer and reduction of pain through aerobic exercise.
Methods: This study was a cross-sectional candidate gene association analysis secondary to the EPICC study, a randomized controlled trial examining the effects of aerobic exercise on cognitive function in women diagnosed with breast cancer who will undergo AI therapy. This study's genetic analysis examined the methylation and genetic variability of the BDNF gene, and pain. Pain scores were observed at enrollment, time point 1 (TP1) and time point 2 (TP2), 6 months after usual care or the structured aerobic exercise intervention. The genotyping for rs6265 was analyzed using an Applied Biosystems ™ QuantStudio™ 3 Real-Time PCR System. DNA methylation data for the BDNF gene was taken from the whole genome DNA methylation data collected using the Illumina Infinium Methylation EPIC Beadchip from the two-time points. The pain scores were assessed at the two time points using the Brief Pain Inventory (BPI) and worst pain scores were used for final analysis.
Results: The sample (n=116) consisted of post-menopausal women with an average age of 62 years old. The genotype analyses found a greater percent decrease in reported pain levels in those in the intervention group than those in usual care, with a larger decrease in pain scores found in the homozygous wild type allele (CC) than those who belong to the heterozygous (CT) and homozygous variant (TT). The methylation analysis supports the relationship between increasing BDNF methylation and decrease in pain scores.
Discussion: This study found that rs6265 CC homozygotes, which corresponds to being a Val/Val homozygote, as well as increasing methylation, were associated with decreased pain in postmenopausal women with early-stage breast cancer, particularly in those randomized to the exercise intervention. These findings are consistent with the literature for non-cancer patients.
Conclusion: Our hypothesis was supported as this study supports a role for the BDNF gene in pain in postmenopausal women with early-stage breast cancer.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Levy, Sarah D.sal212@pitt.eduSal212
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorConley, Yvetteyconley@pitt.edu
Committee MemberWagner, Monicamaw269@case.edu
Committee MemberBender, Catherinecbe100@pitt.edu
Date: 24 April 2024
Date Type: Publication
Defense Date: 15 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: 42
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: n/a
Date Deposited: 24 Apr 2024 14:58
Last Modified: 24 Apr 2024 14:58
URI: http://d-scholarship.pitt.edu/id/eprint/46205

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