||1R01CA231925-01A1 Interpret this number
||University Of South Alabama
||Impact of Social Factors on Breast Cancer Biology in African-American Women
African American (AA) women are more likely to be diagnosed at an early age with breast cancer (BC), have
aggressive disease and experience greater mortality, compared to their Caucasian American (CA) counterparts.
Socioeconomic status (SES) and social stress have long been believed to be the prime cause of such health
disparities; however, it is not yet well understood how these social factors are translated into increased cancer
risk, aggressive tumor-subtypes, and poor clinical outcomes. Demographic data suggest that AA women
encounter more socioeconomic difficulties than CA women and social stressors impact human biology through
epigenomic modifications of gene functions. MicroRNAs, which are important epigenetic modulators of gene
expression and key players in human biology and disease, are known to be regulated by stress
hormones/cytokines and exhibit differential expression in socially disadvantaged population. Along these lines,
our published and preliminary studies have identified increased serum levels of inflammatory cytokines and
stress hormones (resistin, IL6, leptin, and cortisol), and certain microRNAs (miR-511, miR-27a, and miR-33a) in
AA women (with or without BC). We have also observed that treatment of BC cells and macrophages with
resistin, IL6, leptin, and cortisol leads to an upregulation of miR-511, miR-27a, and miR-33a, promotes growth
and malignant behavior of BC cells, and induces M2 polarization of macrophages. These compelling findings
build a strong scientific premise for this project and support our hypothesis that socioeconomic hardships
promote chronic inflammation and stress leading to altered serum levels of hormones and cytokines (such as
resistin, IL6, leptin, and cortisol), which in turn, modulate the expression of immune-suppressive and tumor-
promoting miRNAs, eventually contributing to BC pathogenesis. In four specific aims, we propose to determine
global changes in circulating microRNAs in serum of AA and CA women (with or without BC) and establish their
correlation with SES (low/moderate/high) (Aim 1); analyze levels of resistin, IL6, leptin, and cortisol in serum,
and study their association with SES and serum miRNAs (Aim 2); examine regulation of miRNAs by resistin, IL6,
leptin, and cortisol and delineate the underlying mechanisms (Aim 3); and establish the pathobiological
significance of differentially-expressed miRNAs (Aim 4). Together, these studies will establish the functional
association between socioeconomic health determinants and breast tumor biology, and support the role of
miRNAs as epigenomic modifiers that link the social stress to biological phenotypes.
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