||5R01CA260615-03 Interpret this number
||University Of California-Irvine
||Determinants of the Racial/Ethnic Disparity in Mgus Risk: an Epidemiologic Study in 4 Cohorts
Multiple myeloma (MM) is the second most common hematological malignancy and is largely incurable. Black
Americans experience an unexplained 2-fold excess risk compared to White Americans, while Asian Americans
experience a lower risk. MM is preceded by a precursor state characterized by an accumulation of benign
monoclonal plasma cells that secrete a monoclonal protein (monoclonal gammopathy of undetermined
significance, MGUS), which occurs with the same racial/ethnic disparity as seen in MM. Thus, explaining the
causes of the disparity in MGUS will shed light on the causes of the disparity in MM. We (MPIs Cozen, Desai
and Bertrand) are submitting this proposal in response to PAR 19-279, MMDPQ1: “What risk factors, singularly
or in cooperation, explain the variation in MGUS incidence among different races?” Our central hypothesis is
that racial and ethnic differences in plasma cell growth/angiogenic factors, microbial translocation, chronic
antigenic stimulation due to previous infection and lifestyle factors can explain the observed MGUS incidence
disparity. By screening participants in 4 multiethnic NCI epidemiology cohorts (Black Women's Health Study,
Women's Health Initiative, Multiethnic Cohort, Southern Community Cohort Study), we will identify 844 Blacks,
844 Non-Latino Whites, 146 Latino and 146 Asians with laboratory validated MGUS and an equal number of
age-, sex- race/ethnicity- matched controls without MGUS by the same laboratory screening. We will measure
levels of 18 biomarkers reflecting plasma cell growth, angiogenesis, inflammation and microbial translocation
(IL6, IL17, XCL13, IL6-R, BAFF, APRIL, gp130, HGF, CCL-8, Angioprotein-2, LBP, sCD14, adiponectin, BCMA,
IP-10, IL10, MIP1-a, CXCL12) (Aim 1). We will also examine exposures associated with B-cell activation
including lifetime cumulative infection from chronic immune stimulating agents by measuring antibodies
simultaneously in a multiplex system to Hepatitis B and C viruses, H. pylori, T. gondii, T. pallidum, C. trachomatis,
HPV, and all 8 Herpes family viruses (Aim 2), and lifestyle factors obesity, physical activity, diabetes and use of
anti-inflammatory medications metformin, statins and aspirin, known to affect B-cell response (Aim 3). To
determine whether a given putative risk factor can (at least partly) explain the racial disparities in MGUS we will
(1) determine whether the factor is consistently related to MGUS within all four ethnic groups and if so then; (2)
estimate the strength of the relationship in a combined analysis and; (3) determine whether the prevalence of an
MGUS-associated factor differs by race in a direction consistent with the known racial differences in MGUS risk.
We will use logistic regression techniques that relate either continuous or binary factors (body mass index,
diabetes, individual infections) to the log odds of MGUS. With our multidisciplinary team of co-investigators and
collaboration of 4 racially/ethnically diverse cancer epidemiology cohorts, we are uniquely positioned to be able
to identify causes of the MGUS disparity, about which there is little known. This study will provide critical
information on the knowledge gap that exists in the causes of racial/ethnic disparity for MGUS.
Vitamin D and monoclonal gammopathy of undetermined significance (MGUS) among U.S. Black women.
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Journal of cellular biochemistry, 2019 Jul; 120(7), p. 10952-10955.