Prevalance and Progression of Monoclonal Gammopathies

单克隆丙种球蛋白病的患病率和进展

• 批准号: 7771755
• 负责人: S VINCENT RAJKUMAR
• 金额: $ 30.25万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7771755
• 关键词: Address; Affect; Age; Anemia; Architecture; Archives; Biological Assay; Blood; Blood specimen; Bone Marrow; Cancerous; Cells; Clinic; Clinical; Clinical Trials Design; Coin; Collection; Country; County; Coupled; Data; Databases; Deuterium Oxide; Diagnosis; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Equilibrium; Ethnic Origin; Ethnic group; Etiology; Event; Family; Family member; First Degree Relative; Funding; Future; General Population; Genes; Genetic; Genetic Predisposition to Disease; Goals; Grant; Health; Heavy-Chain Immunoglobulins; High Resolution Computed Tomography; Hispanics; Human; Hypercalcemia; Immunoglobulins; Individual; Infection; Inherited; Institution; Interleukin-1 beta; Intervention; Kidney Failure; Label; Laboratories; Lesion; Life; Life Style; Light; Light-Chain Immunoglobulins; Link; Lytic; Malignant - descriptor; Malignant Neoplasms; Marrow; Measurement; Measures; Mediator of activation protein; Minnesota; Minority; Molecular Genetics; Monoclonal Gammapathies; Monoclonal gammopathy of uncertain significance; Multiple Myeloma; Natural History; Newly Diagnosed; Non-Malignant; Not Hispanic or Latino; Nutritional; Obesity; Outcome; Pathogenesis; Patients; Peripheral; Plasma Cells; Play; Population; Precancerous Conditions; Predisposing Factor; Predisposition; Premalignant; Prevalence; Preventive; Preventive Intervention; Race; Recruitment Activity; Relative (related person); Resolution; Risk; Risk Factors; Role; Sampling; Scanning; Serum; Staging; Surveys; Survival Rate; Techniques; Testing; Thalidomide; Time; Toxin; United States; Variant; X-Ray Computed Tomography; base; bone; cohort; follow-up; genetic linkage; improved; insight; lifestyle factors; member; multiple myeloma M Protein; neoplastic cell; novel; outcome forecast; population based; prevent; proband; programs; public health relevance; racial and ethnic; trait

DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a plasma cell malignancy that evolves from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). Our earlier studies show that MGUS is prevalent in over 3% of the population = age 50. We have identified several risk factors for MGUS progression, and have also found a possible increased risk of the condition in first-degree relatives. Since MM is a devastating, incurable malignancy, the essential aspects of our program are to identify and characterize etiologic factors for MGUS, and risk factors for its progression to MM. We have identified four crucial questions to be addressed: 1) what extent do racial and ethnic factors affect the occurrence of MGUS? 2) what role do genetic and environmental risk-factors play in the causation of MGUS? 3) What are new predictors of progression of MGUS to MM? and 4) what is the prognosis of light chain MGUS (LC-MGUS), a poorly a new entity we defined in the last funding period? Our Specific Aims correspond to these 4 questions. In Aim 1, we will estimate the differential prevalence of MGUS by race and ethnicity in the US, and study potential risk factors by using blood samples and extensive demographic and laboratory data from the National Health and Nutritional Examination Survey (NHANES) that we have acquired. In Aim 2, we will confirm the increased prevalence of MGUS in first-degree relatives, and examine the influence of environmental risk factors on familial MGUS. In Aim 3, we seek to identify improved predictors of progression of MGUS to MM, specifically testing 4 hypothesis-driven risk factors that can be assessed using novel laboratory tests. These include worsening of serum free light chain ratio over time, high-resolution peripheral quantitative computed tomography (HRpQCT) scans to assess micro-architectural changes in bone, heavy water labeling studies to determine plasma cell proliferative rate in MGUS, and measurement of light-chain isotype specific quantitative immunoglobulin levels using the new serum immunoglobulin heavy chain assay (Hevylite). In Aim 4, we will study newly diagnosed patients with LC-MGUS to determine their progression rate and outcome, in the same manner as we did with typical MGUS in prior studies. The proposed studies are critical to addressing fundamental questions concerning the cause of MGUS, its progression to incurable malignancy at a relentless rate of 1% per year, and form the basis for the institution of preventive measures to halt or delay progression. PUBLIC HEALTH RELEVANCE: Monoclonal gammopathy of undetermined significance (MGUS) is probably the most common pre-cancerous condition in the United States affecting over 3% of the population over the age of 50. The studies in this grant seek to answer a fundamental question as to what causes MGUS by studying carefully various racial and ethnic groups, as well as close family members. We also study why (and how) some but not all people with MGUS progress to the fatal cancer called multiple myeloma.

描述（由申请人提供）：多发性骨髓瘤（MM）是一种血浆细胞恶性肿瘤，它是从未定义显着性（MGUS）的称为单克隆性伽马病（MGUS）的单克隆性伽马病（MGUS）演变而来的。我们较早的研究表明，MGU在3％以上的人口= 50岁的人口中很普遍。我们已经确定了MGUS进展的几个风险因素，并且还发现一级亲属中可能会增加这种状况的风险。由于MM是一个破坏性的，无法治愈的恶性肿瘤，因此我们计划的基本方面是识别和表征MGU的病因学因素，以及其发展为MM的风险因素。我们已经确定了要解决的四个关键问题：1）种族和种族因素在多大程度上影响MGU的发生？ 2）遗传和环境风险因素在MGU的因果关系中起什么作用？ 3）MGU向MM进展的新预测指标是什么？ 4）轻链MGU（LC-MGUS）的预后是什么，这是我们在上一个资金期间定义的一个新实体的差？我们的具体目标对应于这4个问题。在AIM 1中，我们将估算美国种族和种族对MGU的差异流行率，并通过使用血液样本以及我们已获得的国家健康和营养检查调查（NHANES）的大量人口统计学和实验室数据来研究潜在的危险因素。在AIM 2中，我们将确认MGU在一级亲戚中的患病率增加，并检查环境危险因素对家族MGU的影响。在AIM 3中，我们试图确定MGU向MM进展的改进预测指标，专门测试了可以使用新型实验室测试评估的4个假设驱动的危险因素。这些包括随着时间的流逝，血清游离光链比率恶化，高分辨率外围定量计算机断层扫描（HRPQCT）扫描，以评估骨骼中的微体积变化，重型水标记研究，以确定MGU中的浆细胞增殖速率，以及使用轻型型均匀型均等型均等型均衡量构型均等型均衡量的衡量序列型均等型均等型均等量封闭量的衡量。 （Hevylite）。在AIM 4中，我们将研究新诊断的LC-MGU患者，以确定其进展率和结果，就像在先前的研究中与典型的MGU一样。拟议的研究对于解决有关MGU原因的基本问题至关重要，其发展为每年1％的不懈态度的恶性肿瘤，并为制定预防措施停止或延迟进展的基础是基础。公共卫生相关性：不确定意义（MGU）的单克隆性伽马病（MGU）可能是美国最常见的癌前状况，影响了50岁以上30岁以上人口的3％。该赠款的研究旨在回答一个基本问题，即通过仔细研究MGU来仔细研究各种种族和种族群体，以及关闭家庭成员。我们还研究了为什么（以及不是所有患有MGU的人）转变为致命癌症的原因，称为多发性骨髓瘤。