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ORCID
N/A
Access Type
Open Access Thesis
Document Type
thesis
Degree Program
Nutrition
Degree Type
Master of Science (M.S.)
Year Degree Awarded
2018
Month Degree Awarded
May
Abstract
Obesity has reached an epidemic level in the United States. A number of epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation informs the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We developed and measured the breast tissue folate by a Lactobacillus Casei microbiological assay, and the DNA methylation of LINE-1, a biomarker of genome-wide methylation, and the promoter methylation and gene expression of SFRP1, a tumor suppressor, were measured by pyrosequencing and real-time PCR. We found a high BMI is associated with increased folate level in the mammary tissue, with an increase of 2.65 ng/g of folate per every 5-unit increase of BMI (p < 0.05). The LINE-1 DNA methylation was significantly associated with BMI (p < 0.05), and marginally associated with folate concentration (p = 0.087). For the 8 CpG sites analyzed in the promoter region of the SFRP1 gene, no associations were observed for either BMI or tissue folate (p > 0.05), although a high expression of SFRP1 was observed in subjects with high BMI or high folate (p < 0.05). This study demonstrated that, in premenopausal women, obesity is associated with an increased mammary folate status, genome-wide DNA methylation and SFRP1 gene expression, indicating that the improved folate and epigenetic status is potentially responsible for the reverse association between obesity and pre-BC. More studies are warranted to further understand how obesity mediates pre-BC via altering folate metabolism and DNA methylation.
DOI
https://doi.org/10.7275/11888562
First Advisor
Zhenhua Liu
Second Advisor
Richard Wood
Recommended Citation
Frederick, Armina-Lyn, "Impact of Bodyweight on Tissue-Specific Folate Status, Genome Wide and Gene-Specific DNA Methylation in Normal Breast Tissues from Premenopausal Women" (2018). Masters Theses. 639.
https://doi.org/10.7275/11888562
https://scholarworks.umass.edu/masters_theses_2/639
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Human and Clinical Nutrition Commons, Medical Molecular Biology Commons, Medical Nutrition Commons, Molecular, Genetic, and Biochemical Nutrition Commons