Support for Infrastructure of Childhood Leukemia Environmental Research

摘要 白血病是最常见的儿童癌症，每年影响全球4万多名儿童。在.期间 在过去的三十年里，儿童白血病(CL)的发病率在美国总体上增加了约35%， 在拉美裔中的上升幅度更大。这种快速的增加在CL的病因中涉及环境因素，可能在 与遗传因素相结合。尽管许多类型的CL的治疗方法有所改善，但幸存者仍面临 严重的并发症。环境因素在CL远期并发症发生中的作用 是未知的。这项建议的总体目标是维护、增强和丰富 NIEHS资助的两项现有的CL环境病例对照研究在不同种族的人群中进行 加州(加州儿童白血病研究；CCLS，1995-2016)和危地马拉(crecerÉStudy；2013- 2015年)。CCLS收集了大量的环境和基因数据，并收集了丰富的 用于多达2213个CL病例和1310个对照的生物检疫和粉尘样本，使其成为最全面的 世界范围内的CL研究。CCLS已经产生了开创性的发现，记录了CL和CL的产前起源 确定导致疾病发展的许多因素，包括：接触化学物质、饮食、 免疫反应和遗传因素。CCLS还支持开发新的实验室方法 对存档的新生儿干血样本进行基因组、表观基因组和暴露全基因组研究。这个 需要维护CCLS资源并加强数据共享程序，才能有效地 扩大正在进行的CL的病因学和肿瘤生物学研究，并开始新的研究 预防、早期发现、干预和生存等领域。我们小组还完成了一项试点工作 危地马拉CL研究，与现有医院合作，纳入50例病例和50例对照 网络，并收集生物菌种以及遗传和环境数据，重点是室内空气 污染。维护这些资源对于支持未来扩展这项脆弱的研究是至关重要的 人口。此外，CCLS--其中45%由拉丁裔儿童组成--和危地马拉的研究将 支持未来致力于确定CL风险中种族差异的原因的项目。这些研究将 还继续作为选定成员之一参加儿童白血病国际联合会 来自世界各地的队列，包括拉丁美洲后裔的儿童。为了实现我们的目标，我们计划 1)管理和管理现有生物标本的库存(例如，骨髓、血液、DBS、唾液、尿液)； 粉尘样本，以及来自医疗记录、访谈、地理信息系统和实验室分析的数据； (2)提升生物库和数据库的能力；(3)通过改进关系数据库来增强数据共享 用于及时数据查询和项目规划的数据库，开发用于跟踪请求的数据库，以及 设计一个数据共享的网站。此外，我们建议通过测量新的生物标志物来丰富CCLS 宫内心理社会应激对免疫功能和CL风险的影响尚不清楚。

ABSTRACT Leukemia is the most common pediatric cancer affecting more than 40,000 children worldwide each year. During the last three decades, childhood leukemia (CL) incidence has increased in the US by ~35% overall, with an even larger rise among Latinos. This rapid increase implicates environmental factors in CL etiology, possibly in combination with genetic factors. Despite improved treatments for many types of CL, survivors remain at risk for serious complications. The role of environmental factors play in the development of long-term CL complications is unknown. The overarching objective of this proposal is to maintain, enhance, and enrich the infrastructure of two existing NIEHS-funded environmental case-control studies of CL conducted in ethnically-diverse populations of California (California Childhood Leukemia Study; CCLS, 1995-2016) and Guatemala (CRECERÉ study; 2013- 2015). The CCLS has collected a wealth of environmental and genetic data, and assembled a rich inventory of biospecimens and dust samples for up to 2213 CL cases and 1310 controls, making it the most comprehensive CL study worldwide. The CCLS has produced seminal findings, documenting the prenatal origin of CL and identifying many factors that contribute to the development of the disease including: chemical exposures, diet, immune response, and genetic factors. CCLS also supported the development of novel laboratory methods for genome-, epigenome-, and exposome-wide studies of archived newborn dried blood specimens. The maintenance of CCLS resources and the enhancement of data sharing procedures are needed to efficiently expand ongoing etiologic and tumor-biology studies of CL and also to begin new studies on emerging research areas such as prevention, early detection, intervention, and survivorship. Our group has also completed a pilot study of CL in Guatemala that enrolled 50 cases and 50 controls in collaboration with established hospital networks, and collected biospecimens as well as genetic and environmental data with a focus on indoor air pollution. Maintaining these resources is critical to support future expansion of the study in this vulnerable population. In addition, the CCLS--45% of which is comprised of Latino children--and the Guatemala study will support future projects dedicated to identifying the causes of the ethnic disparity in CL risk. These studies will also continue to participate in the Childhood Leukemia International Consortium, as one of the select member cohorts from around the world that include children of Latin American descent. To achieve our goal, we plan to 1) curate and manage the inventory of existing biospecimens (e.g., bone marrow, blood, DBS, saliva, urine), dust samples, and data from medical records, interviews, geographic information system, and laboratory assays; (2) upgrade the biorepository and database capabilities, and (3) enhance data sharing by improving the relational databases used for timely data queries and project planning, developing a database for tracking requests, and designing a website for data sharing. In addition, we propose to enrich the CCLS by measuring novel biomarkers of in-utero psychosocial stress for which the impact on immune function and CL risk is unknown.