Determinants of the racial/ethnic disparity in MGUS risk: An epidemiologic study in 4 cohorts

MGUS 风险种族/民族差异的决定因素：4 个队列的流行病学研究

• 批准号: 10491335
• 负责人: Kimberly A Bertrand
• 金额: $ 85万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491335
• 关键词: Activated B-Lymphocyte; Address; Affect; Age; Aging; Angiogenic Factor; Anti-Inflammatory Agents; Antibodies; Antigens; Archives; Asian; Asian Americans; Asian population; Aspirin; B cell differentiation; B-Cell Activation; B-Lymphocytes; Benign; Biological Assay; Biological Markers; Black American; Black Populations; Black race; Body mass index; CXCL10 gene; CXCL12 gene; CXCL13 gene; Chlamydia trachomatis; Chronic; Cohort Studies; Collaborations; Communities; Data; Development; Diabetes Mellitus; Epidemiology; Ethnic Origin; Ethnic group; Exercise; Family; Female; Goals; Growth; Growth Factor; Helicobacter pylori; Hematologic Neoplasms; Hepatitis B; Hepatitis C virus; Hispanic; Hispanic Populations; Human Papillomavirus; IL17 gene; IL6 gene; IL6ST gene; Immune; Immune response; Immunologic Markers; Incidence; Individual; Infection; Infectious Agent; Inflammation; Interleukin-10; Knowledge; Laboratories; Latino; Life Style; Light; Logistic Regressions; Malignant Neoplasms; Measures; Medical Records; Memory; Metformin; Monoclonal gammopathy of uncertain significance; Multiple Myeloma; Nested Case-Control Study; Not Hispanic or Latino; Obesity; Outcome Assessment; Participant; Pharmaceutical Preparations; Physical activity; Plasma Cells; Population; Positioning Attribute; Prevalence; Prevention; Preventive; Proteins; Race; Relative Risks; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Serum; Signal Transduction; Specimen; System; Techniques; Time; Toxoplasma gondii; Treponema pallidum; Variant; Virus; Women' s Health; adiponectin; angiogenesis; black women; cancer epidemiology; cancer health disparity; case control; caucasian American; cell growth; chemokine; chronic infection; cohort; cytokine; epidemiology study; ethnic difference; ethnic diversity; experience; lifestyle factors; male; microbial; multi-ethnic; multidisciplinary; neoplasm registry; racial and ethnic; racial and ethnic disparities; racial determinant; racial difference; racial disparity; racial diversity; response; screening; sex

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.

多发性骨髓瘤（MM）是第二常见的血液系统恶性肿瘤，在很大程度上无法治愈。黑色的 与白人美国人相比，美国人经历了意外的2倍超过风险 体验较低的风险。 MM之前是前体状态，其特征是良性的积累 分泌单克隆蛋白的单克隆浆细胞（不确定的单克隆性γ- 意义，mgus），它以与MM相同的种族/种族差异发生。那就解释了 MGU中差异的原因将阐明MM差异的原因。我们（Mpis Cozen，Desai 和伯特兰德（Bertrand）提交了该提案，以响应于19-279年的MMDPQ1：“有什么风险因素，单一的风险因素 或合作，解释不同种族之间MGUS事件的变化？”我们的中心假设是 浆细胞生长/血管生成因子，微生物易位，慢性的种族和种族差异 由于先前的感染和生活方式因素而引起的抗原刺激可以解释观察到的MGUS入射 差距。通过筛选4个多种族NCI流行病学队列的参与者（黑人妇女健康研究， 妇女健康倡议，多民族队列，南方社区队列研究），我们将确定844个黑人， 844个非拉丁裔白人，146个拉丁裔和146个亚洲人，具有实验室验证的MGU和相等数量的 年龄，性别种族/种族与匹配的控制，没有同一实验室筛查，而无需MGU。我们将衡量 反映浆细胞生长，血管生成，注射和微生物易位的18种生物标志物的水平 （IL6，IL17，XCL13，IL6-R，BAFF，4月，GP130，HGF，CCL-8，血管蛋白-2，LBP，SCD14，SCD14，Adiponectin，adiponectin，BCMA，BCMA，BCMA，BCMA， IP-10，IL10，MIP1-A，CXCL12）（AIM 1）。我们还将检查与B细胞激活相关的暴露 包括通过测量抗体的慢性免疫刺激剂的寿命累积感染 同样，在丙型肝炎和C病毒的多重系统中，幽门螺杆菌，T。 HPV和所有8种疱疹家庭病毒（AIM 2）以及肥胖，体育锻炼，糖尿病和使用的生活方式因素 抗炎药二甲双胍，他汀类药物和阿司匹林，已知会影响B细胞反应（AIM 3）。到 确定给定推定的危险因素（至少部分）是否可以解释MGU中的种族分布，我们将 （1）确定因子是否在所有四个族裔群体中与MGU持续相关，如果是这样。 （2） 在组合分析中估计关系的强度； （3）确定是否患病率 种族与MGUS风险中已知的大鼠差异一致的方向与种族相关的因子差异。 我们将使用与连续或二元因素相关的逻辑回归技术（体重指数， 糖尿病，个体感染）对MGU的对数赔率。与我们的共同投资者的多学科团队和 4个阶段/种族多样化的癌症流行病学队列的合作，我们有独特的位置 确定MGUS差异的原因，鲜为人知。这项研究将提供关键 关于MGU的种族/种族差异原因，有关知识差距的信息。