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.

抽象的 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 在过去的三十年中，美国的童年白血病（CL）的发病率增加了约35％，有 拉丁美洲人的上升甚至更大。这种快速增加在CL病因中实现了环境因素，可能 结合遗传因素。尽管对多种类型的CL的治疗方法有所改善，但生存仍处于风险 严重的并发症。环境因素在长期CL并发症的发展中起着作用 是未知的。该提案的总体目标是维护，增强和丰富 两项现有的NIEHS资助的环境病例对照研究在种族多样性人群中进行的CL 加利福尼亚（加利福尼亚儿童白血病研究； CCLS，1995-2016）和危地马拉（Creceré研究； 2013-- 2015）。 CCLS收集了大量的环境和遗传数据，并组装了丰富的库存 最多2213个CL病例和1310个对照的生物测量和灰尘样品，使其成为最全面的 CL研究全球。 CCLS产生了半调查，记录了CL和 确定许多有助于疾病发展的因素，包括：化学暴露，饮食， 免疫反应和遗传因素。 CCL还支持开发新的实验室方法 基因组，表观基因组和全外科体的研究，对存档的新出生的干血标本的研究。 需要维护CCLS资源和增强数据共享程序才能有效 扩大CL的持续病因和肿瘤生物学研究，并开始有关新兴研究的新研究 诸如预防，早期检测，干预和生存之类的领域。我们的小组还完成了一名飞行员 危地马拉的CL研究与已建立医院合作招募了50例病例和50个对照 网络，收集的生物测量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该研究的未来扩展至关重要 人口。此外，CCLS（其中45％已完成拉丁裔儿童），危地马拉研究将 支持未来的项目，致力于确定CL风险中种族差异的原因。这些研究会 还继续参加儿童白血病国际财团，作为选定成员之一 来自世界各地的人群，包括拉丁美洲血统的孩子。为了实现我们的目标，我们计划 1）策划和管理现有生物测量的清单（例如骨髓，血液，DBS，唾液，尿液）， 灰尘样本以及医疗记录，访谈，地理信息系统和实验室测定的数据； （2）升级生物座和数据库功能，（3）通过改善关系来增强数据共享 用于及时数据查询和项目计划的数据库，开发用于跟踪请求的数据库，以及 设计一个用于数据共享的网站。此外，我们建议通过测量新型生物标志物来丰富CCL 对免疫功能和CL风险的影响尚不清楚的内罗心理压力。

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