R01CA260615

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 Latinos, 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.

Irvine University Of California

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Irvine, California 926970001 United States

Single Zip Code

Provocative Questions (PQs) in Multiple Myeloma Disparities Research (R01 Clinical Trial Optional) (PAR-19-279)

Amendment Since initial award the total obligations have increased 359% from $975,742 to $4,479,852.