Grant Details
Grant Number: |
3U01CA271014-01S1 Interpret this number |
Primary Investigator: |
Vachon, Celine |
Organization: |
Mayo Clinic Rochester |
Project Title: |
Impact of Genetic Susceptibility Along the Continuum From Mgus to Mm (SUPPLEMENT) |
Fiscal Year: |
2022 |
Abstract
ABSTRACT
This application is being submitted in response to the Notice of Special Interest (NOSI), NOT-CA-22-057.
Racial disparities exist for multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined
significance (MGUS); both MGUS and MM are at least twice as common in Black compared with White
populations, including at younger ages. A similar two-fold increase in MGUS has been seen in a population-
based sample of Black men in Ghana compared to a White reference population, suggesting that the disparity
is similar outside of the US. MGUS also is familial, with 2-3-fold increased prevalence in first-degree relatives
of MM or other hematologic malignancies. Although MGUS is usually benign, it is common in those ages 50
and older, progresses to MM or other lymphoproliferative proliferative disorders at rates of 1-1.5% per year,
and is associated with increased risk of infection, fracture, osteoporosis, renal impairment, and thrombosis,
with resultant morbidity and mortality. Thus, understanding the development of MGUS and MGUS progression
to MM is important, particularly among those with the highest risk, including people of African ancestry (AA)
and first-degree relatives of MM and hematologic disorders. Our parent grant (U01 CA271014) proposes a
comprehensive evaluation of genetic susceptibility to MGUS and MGUS progression to MM using established
epidemiologic and genomic studies. Due to the importance of racial predisposition, for the first time, we
propose to evaluate known MM susceptibility variants and identified novel variants for MGUS and MGUS
progression in an AA population (Parent U01, Aim 3). In this supplement application, we establish a new
global collaboration with Dr. Rotimi at Covenant University in Nigeria to conduct complementary studies of
MGUS in West Africa to enhance the genetic investigations of MGUS and MGUS progression among people of
AA. In Aim 1, we will estimate the prevalence of MGUS using a novel mass spectrometry assay, in two
risk groups ages 40 and older in Nigeria [a community-based sample (N=300) and first-degree relatives
of MM and hematologic cancer patients (N=100)] and compare to US population-based rates. This aim
leverages the experience and existing infrastructure of the Prostate Cancer Transatlantic Consortium network
that recruited over 1000 participants and first-degree relatives, including ten Nigerian clinical sites. In Aim 2, we
will conduct genotyping (GWAS) of MM (N=25), MGUS identified through screening Aim 1 samples (N=66),
and a sample of unaffected participants (N=100) to contribute to the validation of genetic risk factors for
MGUS risk and MGUS progression to MM in AA populations, as proposed in our parent U01. Finally, we
will establish a family study of MGUS, MM and related disorders and perform whole exome sequencing on 25
relatives to identify rare variants. Understanding the prevalence of MGUS and genetic determinants of MGUS
and progression will have high impact for West African populations, as life expectancies continue to see a
steady rise, and more individuals will develop MGUS, MM, and other diseases associated with aging.
Publications
None. See parent grant details.