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: 10217882
• 负责人: Kimberly A Bertrand
• 金额: $ 97.57万
• 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/10217882
• 关键词: Activated B-Lymphocyte; Address; Affect; African American; Age; Aging; Angiogenic Factor; Anti-Inflammatory Agents; Antibodies; Antigens; Archives; Asian Americans; Asians; Aspirin; B cell differentiation; B-Cell Activation; B-Lymphocytes; Benign; Biological Assay; Biological Markers; 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; Hispanics; 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 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) 是第二常见的血液恶性肿瘤，并且基本上无法治愈。 与美国白人相比，美国人面临着无法解释的超额风险 2 倍，而亚裔美国人 MM 经历较低风险之前是一个以良性积累为特征的前兆状态。 分泌单克隆蛋白的单克隆浆细胞（未确定的单克隆伽马病） 重要性，MGUS），其发生与 MM 中所见的种族/民族差异相同，因此，解释了这一点。 MGUS 差异的原因将揭示 MM We 差异的原因（MPIs Cozen，Desai。 和 Bertrand）提交此提案是为了回应 PAR 19-279，MMDPQ1：“哪些风险因素，特别是 或者合作解释不同种族之间 MGUS 发病率的差异？” 浆细胞生长/血管生成因子、微生物易位、慢性 由于既往感染和生活方式因素引起的抗原刺激可以解释观察到的 MGUS 发病率 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、多种族队列、南方社区队列研究），我们将确定 844 名黑人， 844 名非拉丁裔白人、146 名拉丁裔和 146 名亚洲人拥有经过实验室验证的 MGUS 和同等数量的 我们将通过同一实验室筛选测量年龄、性别、种族/民族匹配的没有 MGUS 的对照。 反映浆细胞生长、血管生成、炎症和微生物易位的 18 种生物标志物的水平 （IL6、IL17、XCL13、IL6-R、BAFF、APRIL、gp130、HGF、CCL-8、血管蛋白-2、LBP、sCD14、脂联素、BCMA、 IP-10、IL10、MIP1-a、CXCL12）（目标 1）。我们还将检查与 B 细胞激活相关的暴露。 通过测量抗体，包括慢性免疫刺激剂的终生累积感染 同时在多重系统中对抗乙型和丙型肝炎病毒、幽门螺杆菌、弓形虫、梅毒螺旋体、沙眼衣原体、 HPV 和所有 8 种疱疹家族病毒（目标 2），以及生活方式因素肥胖、体力活动、糖尿病和使用 已知会影响 B 细胞反应的抗炎药物二甲双胍、他汀类药物和阿司匹林（目标 3）。 确定给定的假定风险因素是否可以（至少部分）解释 MGUS 中的种族差异，我们将 (1) 确定该因素是否与所有四个种族群体中的 MGUS 一致相关，如果是，则 (2)； 估计综合分析中关系的强度；(3) 确定某种关系是否普遍存在 MGUS 相关因素因种族而异，其方向与已知的 MGUS 风险种族差异一致。 我们将使用与连续或二元因素（体重指数、 糖尿病、个体感染）与 MGUS 的对数赔率，以及我们的多学科联合研究团队的合作。 通过 4 个不同种族/民族的癌症流行病学队列的合作，我们具有独特的优势，能够 以确定 MGUS 差异的原因，而这项研究将提供关键的信息。 有关 MGUS 种族/民族差异原因中存在的知识差距的信息。