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 在过去的几十年里，美国儿童白血病的发病率总体上增加了约35%，增幅甚至更大 在拉丁裔中崛起。在几个拉丁美洲国家也观察到类似的趋势。这一快速增长 指出环境因素在儿童白血病发病中的关键作用，可能是联合作用 有遗传因素。尽管儿童白血病的预后总体上有所改善，但在以下方面存在重大差异 亚型、地区、种族/民族和社会经济地位，白血病幸存者仍然面临严重的 终生的并发症。总而言之，这些观察结果突显了支持更多研究和 预防减少白血病负担和差距。此次U24竞争更新的总体目标是 扩大现有人群研究(这里是病例对照设计)的支持以加速儿童白血病 环境研究和预防，重点是拉丁裔人口。在第一个R24周期(2017-22)中，我们 维护和加强NIEHS资助的两项研究的资源和数据共享 加利福尼亚州、美国和危地马拉的拉丁裔儿童。进一步解决儿童白血病的差距 Latinx，在增加研究团队多样性的同时，我们现在建议(I)包括额外的童年 墨西哥和哥斯达黎加资源不足的白血病研究，(2)协调研究转化/预防 在参与国之间，以及(Iii)与加利福尼亚州和 拉丁美洲。这四项参与的研究共招募了8480例儿童白血病病例和4462名对照， 并收集了丰富的环境/遗传数据和生物标本，提供了最全面的 全球拉丁裔人口中的资源。单独或作为儿童癌症和白血病的一部分 这些研究已经产生了开创性的发现，记录了儿童的产前起源 并确定导致疾病风险增加或降低的许多因素，包括 化学物质暴露、饮食/维生素、母乳喂养、免疫反应、出生体重和遗传因素。这个 需要维护这些资源并加强数据共享程序，以有效地 扩大正在进行的儿童白血病的病因学和肿瘤生物学研究，特别是髓系亚型 在拉丁裔中更常见，并揭示了白血病风险和结果差异的来源。为了实现我们的目标 目标，我们计划(1)使用可互操作的管理系统RedCap来提供统一的支持 管理、协调、储存和共享研究资源；(2)通过以下方式丰富病例对照研究 与人群一级接触潜在致癌剂/混合物的数据库建立联系，以及 社会/建筑环境；(3)通过CLIC联盟促进在国内和国际上更广泛地使用数据， 以及(4)在美国扩大与公众、非专业卫生工作者和卫生专业人员的社区参与 和拉丁美洲国家提高对儿童白血病可预防危险因素的认识。

ABSTRACT Leukemia is the most common pediatric cancer affecting more than 40,000 children worldwide each year. During the last decades, childhood leukemia incidence has increased in the US by ~35% overall, with an even larger rise among LatinX. Similar trends are also observed in several Latin American countries. This rapid increase points to the critical role of environmental factors in the development childhood leukemia, possibly in combination with genetic factors. Despite improved prognosis of childhood leukemia overall, there are major differences by subtype, region, racial/ethnic group, and socio-economic status, and leukemia survivors remain at risk for serious lifelong complications. Altogether, these observations highlight the need to support more research and prevention to reduce leukemia burden and disparity. The overall objective of this U24 competing renewal is to expand the support of existing population studies (here case-control design) to accelerate childhood leukemia environmental research and prevention, with a focus on LatinX populations. In the first R24 cycle (2017-22), we maintained and enhanced the resources and data sharing of two NIEHS-funded studies with large numbers of LatinX children in California, United States and Guatemala. To further address childhood leukemia disparity in LatinX, while increasing diversity of the research team, we now propose to (i) include additional childhood leukemia studies with low-resources in Mexico and Costa Rica, (ii) coordinate research translation/prevention among participating countries, and (iii) collaborate with LatinX researchers and health workers in California and Latin America. The four participating studies have enrolled 8,480 childhood leukemia cases and 4,462 controls, and have collected a wealth of environmental/genetic data and biospecimens providing the most comprehensive resources in LatinX populations worldwide. Individually or as part of the Childhood Cancer and Leukemia Consortium (CLIC), these studies have produced seminal findings, documenting the prenatal origin of childhood leukemia and identifying many factors that contribute to the increased or decreased risks of the disease including chemical exposures, diet/vitamins, breastfeeding, immune response, birthweight and genetic factors. The maintenance of these resources and the enhancement of data sharing procedures are needed to efficiently expand ongoing etiologic and tumor-biology studies of childhood leukemia, especially myeloid subtypes which are more common in LatinX, and uncover sources of disparity in leukemia risk and outcomes. To achieve our goals, we plan to (1) use an interoperable management system REDCap to provide unifying support for management, harmonization, storage and sharing of study resources; (2) enrich case-control studies by conducting linkages to population-level databases on exposures to potential carcinogenic agents/mixtures and social/built environments; (3) facilitate broader data use nationally and internationally with the CLIC Consortium, and (4) expand community engagement with the public, lay health workers, and health professionals in the US and Latin American countries to increase awareness about preventable risk factors of childhood leukemia.