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Epigenetic contribution to the excess risk of MGUS in African Americans

Award Number: U01CA249955
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/13/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Epigenetic contribution to the excess risk of MGUS in African Americans - ABSTRACT The goal of this investigation is to characterize the influence of the DNA methylome central to the increased risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) observed in African Americans compared to European Americans. To facilitate an improved understanding of the epigenetic modifications underlying the disparate trends in MGUS risk observed by race, we will address MMDPQ1: What risk factors, singularly or in cooperation, explain the variation in monoclonal gammopathy of undetermined significance (MGUS) incidence among different races? MGUS precedes Multiple Myeloma (MM), which is the most common blood cancer affecting African Americans, characterized by cellular resistance to apoptosis leading to prolonged survival and accumulation of clonally expanded, cytogenetically heterogeneous, antibody producing tumor cells in the bone marrow and extramedullary sites. Risk of MGUS is 2- to 3-fold higher among African Americans compared to European Americans and beyond a few well-established risk factors (race, male sex, obesity, family history of lymphoid malignancy) little is known about the observed disparity in MGUS risk. Although, evidence suggests a germline component, inherited alterations in DNA sequence alone does not explain the disparity. Advances in epigenomics offer new opportunities to characterize the heritable changes in gene activity, or plasticity in germline variation due to past environmental exposures, which could significantly improve our understanding MGUS etiology, differences by ancestry and provide new insight for improved clinical monitoring in high-risk populations. We will test the overarching hypothesis that distinct methylome signatures correlate with the excess risk of MGUS observed in African Americans and that aberrant epigenetic modification influences the disparity in risk by altering target gene expression. Using an epigenome-wide approach, we will capitalize on a unique opportunity to explore differentially methylated positions in DNA obtained from a network of well-characterized, treatment naïve populations of MGUS and MM while taking advantage of recent technological and analytic advances. This project leverages existing partnerships, resources and comprehensive, high-quality clinical data and biospecimens systematically collected in a well-characterized network of treatment-naïve populations, to improve our understanding of the disparate trends in MGUS risk observed by race and to advance a set of biomarkers required to improve efforts to predict and manage MGUS clinical course in high-risk African American populations.


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: 2024 ( Subtotal = $585,460 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	4	5/1/2024	NON-COMPETING CONTINUATION	$585,460
														Subtotal = $585,460

Issue Date FY: 2023 ( Subtotal = $596,783 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	3	7/21/2023	NON-COMPETING CONTINUATION	$596,783
														Subtotal = $596,783

Issue Date FY: 2022 ( Subtotal = $603,947 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	2	9/16/2022	NON-COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	2	4/28/2022	NON-COMPETING CONTINUATION	$603,947
														Subtotal = $603,947

Issue Date FY: 2021 ( Subtotal = $616,274 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	000	1	5/13/2021	NEW	$616,274
														Subtotal = $616,274

Grand Total All Awards = $2,402,464

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Epigenetic contribution to the excess risk of MGUS in African Americans

Award Number: U01CA249955

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/13/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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