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Impact of social factors on breast cancer biology in African-American women

Award Number: R01CA231925
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Impact of social factors on breast cancer biology in African-American women - Contact PD/PI: Singh, Seema ABSTRACT 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. Page 6 Project Summary/Abstract


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	004	6	5/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	001	6	3/19/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$354,207
2025	2023	UNIVERSITY OF SOUTH ALABAMA	307 N UNIVERSITY BLVD	MOBILE	AL	36608	MOBILE	USA	Cancer Cause and Prevention Research	000	5	3/18/2025	NON-COMPETING CONTINUATION	-$354,207
2025	2023	UNIVERSITY OF SOUTH ALABAMA	307 N UNIVERSITY BLVD	MOBILE	AL	36608	MOBILE	USA	Cancer Cause and Prevention Research	002	5	4/22/2025	NON-COMPETING CONTINUATION	-$68
2025	2023	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	003	6	4/22/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$68
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $605,875 )
2023	2023	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Cancer Cause and Prevention Research	000	5	6/27/2023	NON-COMPETING CONTINUATION	$605,875
														Subtotal = $605,875

Issue Date FY: 2022 ( Subtotal = $591,518 )
2022	2022	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Cancer Cause and Prevention Research	000	4	6/7/2022	NON-COMPETING CONTINUATION	$591,518
														Subtotal = $591,518

Issue Date FY: 2021 ( Subtotal = $603,591 )
2021	2021	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Cancer Cause and Prevention Research	000	3	6/3/2021	NON-COMPETING CONTINUATION	$603,591
														Subtotal = $603,591

Issue Date FY: 2020 ( Subtotal = $603,591 )
2020	2020	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Cancer Cause and Prevention Research	000	2	7/9/2020	NON-COMPETING CONTINUATION	$603,591
														Subtotal = $603,591

Issue Date FY: 2019 ( Subtotal = $618,241 )
2019	2019	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Cancer Cause and Prevention Research	000	1	6/28/2019	NEW	$618,241
														Subtotal = $618,241

Grand Total All Awards = $3,022,816

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Impact of social factors on breast cancer biology in African-American women

Award Number: R01CA231925

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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