Myeloma Precursor Disease among WTC responders

WTC 响应者中的骨髓瘤前驱疾病

• 批准号: 10064268
• 负责人: Carl Ola Landgren
• 金额: $ 49.26万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064268
• 关键词: Myeloma; Precursor; Disease; among; WTC

Project Summary/Abstract Hazardous materials including known and suspected carcinogens, were present at the World Trade Center (WTC) disaster site.1,2 For example, some carcinogens present at the WTC disaster site have been found to be associated with multiple myeloma and its precursor disease, in veterans of the Vietnam War exposed to Agent Orange. Recently, in a screening study for multiple myeloma precursor disease, the prevalence of overall monoclonal gammopathy of undetermined significance (MGUS) among WTC-exposed white male firefighters was significantly greater than the general population (risk ratio [RR]=1.76; 95% CI=1.34, 2.29).3 This association was particularly elevated in light-chain MGUS (RR=3.13; 95% CI=1.99, 4.93).3 Additionally, WTC- exposed firefighters compared with the general population had higher proportions with light chain disease and CD20 positive plasma cells, which are typically associated with poorer prognoses.3 In an effort to broaden current knowledge of the relationship between WTC exposure, MGUS and multiple myeloma, we propose a collaborative effort between the Fire Department of the City of New York (FDNY) and General Responder Cohort at Stony Brook University (GRC-SBU) to conduct sensitive immunophenotyping to detect MGUS by screening non-FDNY rescue-recovery workers and comparing results to determine if there are differences between the two responder cohorts. We will then pool data from the two cohorts to generate a global prevalence estimate for the entire WTC-exposed rescue-recovery population. By expanding MGUS screening beyond white male firefighters, we will assess whether the association between WTC exposure and MGUS applies to a more demographically heterogeneous population. Additionally, this will provide us with a better understanding of the disease pathogenesis in participants exposed to the WTC disaster. Finally, an early workup of MGUS can provide potentially disease-modifying therapeutic interventions. This study will allow us to realize the NIOSH WTC Health Program's “Research to Care” translational model. Specifically we aim to 1) To analyze the precursor state of multiple myeloma, MGUS, among WTC-exposed GRC-SBU participants and to compare the prevalence among white males to WTC-exposed white male FDNY firefighters; and 2) To compare the prevalence of MGUS among the combined WTC-exposed responder cohorts (both FDNY and GRC-SBU) to published estimates in population-based studies.

项目摘要/摘要 世界贸易中心出现了包括已知和疑似致癌物在内的危险材料 （WTC）灾难网站。1,2例如，发现WTC灾难网站上存在的一些致癌物是 与多发性骨髓瘤及其前体病有关，在越南战争的退伍军人中 橙子。最近，在一项针对多发性骨髓瘤前体病的筛查研究中，总体流行率 WTC暴露的白人男性消防员中未定意义（MGU）的单克隆性伽马病（MGU） 95％CI = 1.34，2.29）.3 在轻链MGU中的关联升高（RR = 3.13; 95％CI = 1.99，4.93）.3此外，WTC- 与普通人群相比，暴露的消防员在轻链疾病和 CD20阳性浆细胞，通常与较差的预后相关。3 为了扩大当前对WTC暴露，MGU和多重接触之间关系的了解 骨髓瘤，我们提出了纽约市消防局（FDNY）和 Stony Brook University（GRC-SBU）的一般响应者队列进行敏感的免疫表型 通过筛选非FDNY救援录得的工作人员并比较结果以确定是否在那里来检测MGU 是两个响应者队列之间的差异。然后，我们将从两个队列中汇总数据以生成一个 全球暴露救援恢复人群的全球流行估计。通过扩展mgus 筛查白人男性消防员之外，我们将评估WTC暴露与 MGU适用于人口更异质的人群。此外，这将为我们提供 更好地了解暴露于WTC灾难的参与者中的疾病发病机理。最后，早 MGU的检查可以提供潜在的改善疾病的治疗干预措施。这项研究将使我们 实现NIOSH WTC健康计划的“护理研究”翻译模型。 具体而言，我们的目的是1）分析wtc暴露的多发性骨髓瘤的前体状态 GRC-SBU参与者并比较白人男性的患病率与暴露于WTC的白人男性FDNY 消防员； 2）比较合并的WTC响应者中MGU的患病率 同类（FDNY和GRC-SBU）在基于人群的研究中发表的估计值。