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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R21CA155951-02 Interpret this number
Primary Investigator: Brown, Elizabeth
Organization: University Of Alabama At Birmingham
Project Title: A Genome-Wide Methylation Study of Epigenetic Contributions to Multiple Myeloma
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): The goal of this Exploratory/Developmental study is to identify DNA methylation (DNAm) profiles from across the epigenome that contribute to multiple myeloma (MM) pathogenesis. The hypothesis is that epigenomic modification in DNAm profiles is associated with altered risk of MM and among patients with MM, modifications in DNAm contribute to the excess risk observed among African Americans. To test this hypothesis, we intend to (1) compare genome-wide methylation (GWM) profiles in MM cases and controls from >450,000 CpGs in the human genome, using the Illumina Methyl450K analysis using a case-control approach stratified by European American and African American race/ethnicity, (2) compare GWM profiles in three cell types important for MM including CD138+ myeloma "tumor" cells from the bone marrow, endothelial cells from the bone marrow microenvironment and primary lymphocytes from the peripheral blood using a case-only approach and (3) compare GWM profiles between European American and African American cases of MM by cell type using a case-only approach. The extensive characterization of the MM phenotype and related risk factors from existing well-characterized populations coupled with a genome-wide approach that capitalizes on the expertise of our multidisciplinary investigative team will facilitate a rigorous and comprehensive evaluation of the effect of DNAm on MM risk that is disproportionately higher among African Americans. As the experimental relationships described in this application are characterized, we will be well-poised to facilitate biomarker discovery that can be applied to large or at-risk populations in a non-invasive and cost-effective manner. Our approach offers the best opportunity to identify novel epigenetic relationships with MM and to generate preliminary data necessary to investigate functional genomics as a tool for targeting high-risk populations who may benefit from individualized clinical management or therapeutic intervention.

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Publications

A Pooled Analysis Of Reproductive Factors, Exogenous Hormone Use, And Risk Of Multiple Myeloma Among Women In The International Multiple Myeloma Consortium
Authors: Costas L. , Lambert B.H. , Birmann B.M. , Moysich K.B. , De Roos A.J. , Hofmann J.N. , Baris D. , Wang S.S. , Camp N.J. , Tricot G. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jan; 25(1), p. 217-21.
PMID: 26464426
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Family History Of Hematologic Malignancies And Risk Of Multiple Myeloma: Differences By Race And Clinical Features
Authors: VanValkenburg M.E. , Pruitt G.I. , Brill I.K. , Costa L. , Ehtsham M. , Justement I.T. , Innis-Shelton R.D. , Salzman D. , Reddy E.S. , Godby K.N. , et al. .
Source: Cancer Causes & Control : Ccc, 2016 Jan; 27(1), p. 81-91.
PMID: 26596855
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