Support for Infrastructure of Childhood Leukemia Environmental Research

支持儿童白血病环境研究基础设施

• 批准号: 10172904
• 负责人: Catherine Metayer
• 金额: $ 36.69万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172904
• 关键词: Affect; Archives; Area; Biological Assay; Biological Markers; Biological Specimen database; Birth; Blood; Blood specimen; Bone Marrow; California; Case-Control Studies; Chemical Exposure; Chemicals; Child; Childhood Leukemia; Collaborations; Collection; Crime; DNA; Data; Databases; Development; Diagnostic; Diet; Disease; Dust; Early Diagnosis; Enrollment; Environment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Equipment and supply inventories; Etiology; Exposure to; Funding; Future; Genetic; Genetic study; Genome; Geographic Information Systems; Goals; Guatemala; Guatemalan; Health; Hospitals; House Dust; Immune; Immune response; Incidence; Indoor Air Pollution; Infrastructure; International; Intervention; Interview; Joints; Laboratories; Latin American; Latino; Length; Life Experience; Link; Maintenance; Malignant Childhood Neoplasm; Measures; Medical Records; Methods; Mothers; National Institute of Environmental Health Sciences; Neighborhoods; Newborn Infant; Obesity; Pilot Projects; Play; Population; Population Heterogeneity; Poverty; Pregnancy; Prevention; Procedures; Psychosocial Stress; Registries; Research; Research Personnel; Resource Sharing; Resources; Risk; Role; Saliva; Sampling; Seminal; Spottings; Stress; Survivors; Time; Tumor Biology; Urine; Viral; Vital Status; Vulnerable Populations; cohort; data resource; data sharing; design; epidemiology study; epigenome; epigenomics; ethnic disparity; ethnic diversity; fetal; gene environment interaction; genome-wide; high dimensionality; immune function; improved; in utero; indoor exposure; indoor pollutant; leukemia; member; molecular subtypes; nervous system disorder; novel; novel marker; prenatal; preservation; prospective; relational database; reproductive system disorder; research study; survivorship; telomere; time use; trend; web site

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.

摘要 白血病是最常见的儿科癌症，每年影响全球40，000多名儿童。期间 在过去的三十年里，美国儿童白血病（CL）的发病率总体上增加了约35%， 在拉丁美洲人中的上升幅度更大。这种快速增加暗示了CL病因学中的环境因素，可能是 结合遗传因素。尽管许多类型的CL的治疗方法得到了改善，但幸存者仍然面临着以下风险： 严重并发症。环境因素在CL长期并发症发生中的作用 不明本提案的总体目标是维护、加强和丰富 两项现有的NIEHS资助的CL环境病例对照研究在不同种族人群中进行 加州（加州儿童白血病研究; CCLS，1995-2016年）和危地马拉（CRECERTOS研究; 2013- 2015年）。CCLS收集了大量的环境和遗传数据，并汇编了丰富的 多达2213例CL病例和1310例对照的生物标本和灰尘样本，使其成为最全面的 全球CL研究。CCLS已经产生了开创性的发现，记录了CL的产前起源， 确定导致疾病发展的许多因素，包括：化学品暴露，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标本进行基因组、表观基因组和全基因组研究。的 需要维护CCLS资源并加强数据共享程序， 扩大正在进行的CL病因学和肿瘤生物学研究，并开始对新兴研究的新研究 预防、早期发现、干预和生存等领域。我们小组还完成了一个试点 危地马拉CL研究，与现有医院合作，入组50例病例和50例对照 收集的生物标本以及遗传和环境数据，重点是室内空气 污染维持这些资源对于支持未来在这一脆弱地区扩大研究至关重要。 人口此外，CCLS-其中45%是由拉丁裔儿童组成-和危地马拉的研究将 支持未来致力于确定CL风险种族差异原因的项目。这些研究将 我也继续参与儿童白血病国际联盟，作为其中一个选择成员 来自世界各地的群体，包括拉丁美洲血统的儿童。为了实现我们的目标，我们计划 1)策划和管理现有生物样本的库存（例如，骨髓、血液、DBS、唾液、尿液）， 灰尘样本，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)升级生物储存库和数据库能力，以及（3）通过改善关系 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 子宫内心理社会应激对免疫功能和CL风险的影响尚不清楚。

项目成果

Allergies and Childhood Acute Lymphoblastic Leukemia: A Case-Control Study and Meta-analysis.

• DOI: 10.1158/1055-9965.epi-17-0584
• 发表时间: 2018-10
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Wallace AD;Francis SS;Ma X;McKean-Cowdin R;Selvin S;Whitehead TP;Barcellos LF;Kang AY;Morimoto L;Moore TB;Wiemels JL;Metayer C
• 通讯作者: Metayer C

Untargeted adductomics of Cys34 modifications to human serum albumin in newborn dried blood spots.

新生儿干血斑中 Cys34 修饰对人血清白蛋白的非靶向加合组学。

• DOI: 10.1007/s00216-019-01675-8
• 发表时间: 2019
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Yano,Yukiko;Grigoryan,Hasmik;Schiffman,Courtney;Edmands,William;Petrick,Lauren;Hall,Katie;Whitehead,Todd;Metayer,Catherine;Dudoit,Sandrine;Rappaport,Stephen
• 通讯作者: Rappaport,Stephen

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium.

• DOI: 10.1016/j.canep.2019.01.022
• 发表时间: 2019-04
• 期刊: Cancer epidemiology
• 影响因子: 2.6
• 作者: P. Panagopoulou;A. Skalkidou;E. Marcotte;Friederike Erdmann;Xiaomei Ma;J. Heck;A. Auvinen;B. Mueller;L. Spector;E. Roman;C. Metayer;C. Magnani;M. S. Pombo-de-Oliveira;M. Scheurer;A. Mora;J. Dockerty;J. Hansen;Alice Y Kang;Rong Wang;D. Doody;E. Kane;J. Schüz;Christos Christodoulakis;E. Ntzani;E. Petridou

BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia.

• DOI: 10.1002/ijc.31622
• 发表时间: 2018-12-01
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: de Smith AJ;Walsh KM;Francis SS;Zhang C;Hansen HM;Smirnov I;Morimoto L;Whitehead TP;Kang A;Shao X;Barcellos LF;McKean-Cowdin R;Zhang L;Fu C;Wang R;Yu H;Hoh J;Dewan AT;Metayer C;Ma X;Wiemels JL
• 通讯作者: Wiemels JL