Date of Award

1-1-2018

Embargo Period

4-25-2023

Document Type

Thesis

Degree Name

Master of Biomedical Science

Department

Pathology and Laboratory Medicine

College

College of Graduate Studies

First Advisor

David P. Turner

Second Advisor

Victoria J. Findlay

Third Advisor

Laura Spruill

Fourth Advisor

Robin C. Muise-Helmericks

Abstract

African Americans have highest death rate in prostate and breast cancers (BCa), Socioeconomic and environmental risk factors are known to contribute to cancer health disparity [1-5]. Such factors possibly altering cell signaling and gene expression to alter tumor development and progression. To examine the effects of disparity risk factors we need to develop innovative molecular models to test working hypotheses of the biological effects of disparity risk factors and develop potential treatments. Glycation is the non-enzymatic addition of sugar moieties to biological macromolecules which leads to the formation of reactive metabolites known as Advanced Glycation End products (AGEs). AGE accumulation is also associated with the factors that drive cancer disparity. We previously published that the food related AGE Nε -(Carboxymethyl) lysine (CML) is significantly higher in AA compared with EA PCa patients [6]. This study was two-fold: 1) To generate race specific primary cell culture models this can mimic the tumor microenvironment to successfully demonstrate ancestry specific differences in tumor biology. Patient matched epithelial and stromal cell lines were generated and the luminal, basal or fibroblast fractions for each cell type was characterized for a subset of ancestry specific cell lines. Quntitative real time PCR was used to characterize the cell lines for receptor for AGE (RAGE), androgen receptor (AR), and phosphatase and tensin homolog, (PTEN). 2) To examine the correlation between AGE intake and BCa risk in women included in the Health-AARP Diet and Health study. The aim was to correlate CMLAGE intake, with ancestry, socioeconomic factors, lifestyle and BCa incidence rates. The Cox proportional hazard model (HR), shows significant associations between different socioeconomic factors, CML-AGE in the higher vs. lowest quintiles and the incident rate of BCa. However, no significant relationship between ER and PR status in cancer incidents and CML-AGE intake was observed. By utilizing the race specific cell lines models, we can explore the mechanistic consequences of dietary AGE intake and ancestry on tumor biology. Understanding of the biological implications of lifestyle and ancestry on tumor onset and progression may lead to the design of novel intervention and drug strategies aimed at reducing cancer health disparity.

Rights

All rights reserved. Copyright is held by the author.

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