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 该项目建立在现有的北方加州儿童白血病研究（NCCLS）的基础上， 病例对照研究超过1,000例。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病因学中的作用。我们的目标是研究潜在的作用 苯、多环芳烃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中发挥作用。我们将使用最先进的 风险评估技术，以实现这一目标。我们进一步建议使用基因表达 分析和蛋白质组学，以开发新的生物标志物，帮助分类的病因亚型，这 疾病，并帮助找到其原因（S）。我们的假设是，某些白血病亚型会有特定的 环境原因。具体而言，我们计划：1）将案件查明延长至2009年， 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的特征： 蛋白质组学和基因表达谱; 3）与CDC合作，测量30多种挥发性 患有白血病的儿童的母亲和对照母亲血液中的碳氢化合物（我们将比较这些 测量结果与家庭空气和水采样结果以及过去的替代标志物 使用自我报告的烟草烟雾暴露和估计的交通密度进行VOCs暴露）; 4） 测量苯和萘（一种代表性的PAH）的母亲血清中的蛋白加合物， 与北卡罗来纳州SBRP的Rappaport博士合作的病例和对照;以及，5）测量 不同形式白血病患儿血浆中苯和萘的蛋白加合物， 将这些测量结果与对住户样本进行的化学品接触分析相关联。 这项研究的优点是：a）样本量大; B）广泛的住宅暴露评估; c） 测量病例组和对照组母亲目前和累积暴露于超级基金化学品的情况 d）能够将接触情况与国家健康和营养评估系统数据进行比较; e）能够获得经过仔细处理的 生物样本;以及，f）将尖端的组学技术应用于病例 特征化这些研究应提供新的见解，化学品接触的作用， 儿童白血病的病因学，并产生新的暴露和疾病状态的生物标志物， 用于今后的研究。

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.