Project 1: Biomarkers of Chemical Exposure and Leukemia Risk

项目 1：化学品暴露和白血病风险的生物标志物

• 批准号: 8063131
• 负责人: Patricia A Buffler
• 金额: $ 44.11万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-13 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063131
• 关键词: Air; Aromatic Polycyclic Hydrocarbons; Arts; Benzene; Biological; Biological Markers; Biological Process; Blood; Blood Proteins; Blood specimen; California; Case-Control Studies; Centers for Disease Control and Prevention (U.S.); Chemical Exposure; Chemicals; Child; Childhood Leukemia; Classification; Collaborations; Data; Databases; Disease; Etiology; Exposure to; Funding; Future; Gene Expression; Gene Expression Profiling; Goals; Grant; Home environment; Household; Hydrocarbons; Lymphocyte; Measurement; Measures; Molecular Cytogenetics; Mothers; Myeloid Leukemia; Naphthalene; Naphthalenes; National Health and Nutrition Examination Survey; National Institute of Environmental Health Sciences; North Carolina; Patient Self-Report; Plasma; Play; Post-Translational Protein Processing; Proteins; Proteomics; Risk; Role; Sample Size; Sampling; Serum; Surrogate Markers; Techniques; Technology; Tobacco smoke; Trichloroethylene; Universities; adduct; case control; density; disorder subtype; environmental chemical; insight; leukemia; superfund chemical; trafficking; water sampling

Project 1: Biomarkers of Chemical Exposure and Leukemia Risk This project builds upon the existing Northern California Childhood Leukemia Study (NCCLS), a large case-control study with over 1,000 cases. Its overall goal is to determine the role exposure to environmental chemicals plays in the etiology of childhood leukemia. We aim to examine the potential role benzene, polycyclic aromatic hydrocarbons (PAH) and other selected Superfund chemicals, such as trichloroethylene (TCE), play in the etiology of childhood leukemia in California. We will use state-of-the-art exposure assessment techniques to accomplish this goal. We further propose to use gene expression profiling and proteomics to develop new biomarkers that aid in the classification of etiologic subtypes of this disease and help find its cause(s). Our hypothesis is that certain subtypes of leukemia will have specific environmental causes. Specifically, we plan to: 1) Extend case ascertainment through 2009, such that biological samples will be available from over 1000 cases; 2) characterize the childhood leukemia cases by proteomics and gene expression profiling; 3) collaborate with the CDC to measure more than 30 volatile hydrocarbons in the blood of mothers of children with leukemia and control mothers (we will compare these measures with results from concomitant home air and water sampling and with surrogate markers of past exposures to VOCs using self-reported exposure to tobacco smoke and estimated traffic density); 4) measure protein adducts of benzene and naphthalene (a representative PAH) in serum from mothers of cases and controls in collaboration with Dr. Rappaport of the North Carolina SBRP; and, 5) measure protein adducts of benzene and naphthalene in the plasma of children with different forms of leukemia and correlate these measurements with the chemical exposure analysis conducted with household samples. The strengths of the study are: a) Large sample size; b) extensive residential exposure assessment; c) measures of current and cumulative exposure to Superfund chemicals in both case and control mothers and children; d) ability to compare exposures to national NHANES data; e) availability of carefullyprocessed biological samples; and, f) application of sophisticated -omic technologies to case characterization. These studies should provide new insights into the role of chemical exposure in the etiology of childhood leukemia and produce new biomarkers of exposure and disease status that can be used in future studies.

项目1：化学物质暴露与白血病风险的生物标记物 该项目建立在现有的北加州儿童白血病研究(NCCLS)的基础上，该研究是一项大型 1,000多例病例对照研究。其总体目标是确定角色暴露于 环境化学物质在儿童白血病的病因学中起着重要作用。我们的目标是研究潜在的作用 苯、多环芳烃(PAH)和其他选定的超级基金化学品，如 三氯乙烯(TCE)在加州儿童白血病的病因学中发挥着作用。我们将使用最先进的 实现这一目标的暴露评估技术。我们进一步建议使用基因表达 图谱和蛋白质组学开发新的生物标记物，帮助对本病的病因亚型进行分类 并帮助寻找疾病的原因(S)。我们的假设是某些亚型的白血病会有特定的 环境原因。具体地说，我们计划：1)将案件查明延长至2009年，以便 将从1000多个病例中获得生物样本；2)通过以下方式描述儿童白血病病例 蛋白质组学和基因表达谱；3)与疾病预防控制中心合作测量30多种挥发性物质 白血病儿童母亲和对照母亲血液中的碳氢化合物(我们将比较这些 使用伴随家庭空气和水采样的结果以及过去的替代标记物进行测量 使用自我报告的烟草烟雾暴露和估计交通密度暴露于VOCs)；4) 检测婴儿母亲血清中苯和萘(一种具有代表性的多环芳烃)的蛋白质加合物 病例和对照，与北卡罗来纳州SBRP的拉帕波特博士合作；以及，5)测量 不同类型白血病儿童血浆中苯和萘的蛋白加合物 将这些测量与对家庭样本进行的化学暴露分析相关联。 这项研究的优点是：a)样本规模大；b)广泛的住宅暴露评估；c) 病例母亲和对照母亲目前和累积接触超级基金化学品的衡量标准 和儿童；d)比较暴露于国家国民健康保险数据的能力；e)提供经过仔细处理的 生物样本；和(F)将尖端技术应用于案件 人物刻画。这些研究应该会为化学物质暴露在 儿童白血病的病因，并产生新的暴露和疾病状态的生物标志物 在未来的研究中使用。