Early Life Exposures to Air Toxics and the Risk of Early Childhood Leukemia

描述（由申请人提供）：儿童白血病是最常见的儿童癌症，其病因尚不清楚。苯是一种已知的成人白血病致癌物，据推测，接触这种致癌物的环境空气在儿童白血病发病率中起作用，其他空气有毒物质也可能与之有关。这项研究是迄今为止规模最大的研究，旨在评估空气毒性暴露对儿童早期急性髓性白血病（AML）和急性淋巴细胞白血病（ALL）风险的影响。此外，该应用程序的方法学组成部分将严格评估由于从出生到诊断时间的居住变化而导致的暴露分配差异。德克萨斯州提供了一个独特的研究区域来评估与暴露于空气有毒物质有关的癌症风险，因为该州道路交通广泛，石油化工设施和燃煤发电厂数量众多。在健康、社会和经济差距方面，该州在全国排名也很低。将采用病例对照研究设计，控制个人和社区水平的混杂因素。年龄在0-4岁之间的病例将从德克萨斯州癌症登记处和从德克萨斯州出生证明记录中抽样的对照中确定。住宅暴露于空气毒物的评估将使用来自美国环境保护署国家尺度空气毒物评估的苯、1,3-丁二烯和多环芳烃（PAHs）的普查区环境空气水平模型估计。第一个目标是利用模拟的人口普查区苯、1,3-丁二烯和多环芳烃水平估计值，评估ALL和AML风险与环境空气污染之间的关系。这些空气污染物的综合影响也将被评估。由于对环境空气污染和儿童结局的研究往往依赖于出生证明中提供的分娩时母亲的地址来对暴露进行分类，第二个目标将评估基于出生时母亲的地址和诊断时儿童的地址的暴露分配的差异。这项研究具有重要意义，因为它将(1)增强我们对儿童白血病与空气毒性相关的假定风险的理解，(2)帮助流行病学家在未来儿童白血病和其他儿科结局的研究中考虑从出生到诊断的居住流动性的影响。研究结果将为风险评估人员和政策制定者提供有关多种化学压力源产生的综合影响的信息，有助于制定干预措施，以减少与空气污染相关的儿童白血病风险，并为评估因居住流动性而导致暴露错误分类的可能性提供框架。

DESCRIPTION (provided by applicant): The etiology of childhood leukemia, the most common pediatric cancer, remains unknown. Benzene is a known leukemogen in adults and ambient air exposures to this carcinogen have been hypothesized to play a role in the incidence of childhood leukemia and other air toxics may be implicated as well. This investigation will represent the largest study conducted to date to assess effects of air toxic exposures on the risk of early childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Moreover, the methodological component of the application will critically assess differences in exposure assignment due to changes in residence from the time of birth to the time of diagnosis. Texas provides a unique study area to assess cancer risk associated with exposures to air toxics because of its extensive road traffic and the number of petrochemical facilities and coal-fired power plants that operate in the state. The state also ranks poorly in the nation in terms of health, social and economic disparities. A case- control study design with control for individual- and neighborhood-level confounders will be employed. Cases between the ages of 0-4 years will be identified from the Texas Cancer Registry and controls sampled from Texas birth certificate records. Residential exposure to air toxics will be assessed using modeled estimates of census-tract ambient air levels of benzene, 1,3-butadiene and polycyclic aromatic hydrocarbons (PAHs) from the U.S. EPA's National-Scale Air Toxics Assessment. The first aim will be to assess the association between risk of ALL and AML and ambient air pollution using modeled census-tract level estimates of benzene, 1,3- butadiene and PAHs. Combined effects of these air pollutants will also be evaluated. Because studies of ambient air pollution and pediatric outcomes often rely on maternal address at delivery that is available from the birth certificate to classify exposure, the second aim will evaluate differences in exposure assignment based on maternal address at the time of birth and address of the child at the time of diagnosis. The proposed study is significant in that it will (1) enhance our understanding of putative risks o childhood leukemia associated with air toxics and (2) aid epidemiologists in considerations of the impact of residential mobility from birth to diagnosis in future studies of childhood leukemia and other pediatric outcomes. Results will inform risk assessors and policy makers about combined effects arising from multiple chemical stressors, aid in the development of interventions to reduce risks of childhood leukemia associated with air pollution, and provide a framework for evaluating the potential for exposure misclassification due to residential mobility. PUBLIC HEALTH RELEVANCE: This investigation will represent the largest study conducted to date to assess effects of air toxic exposures on the risk of early childhood acute myeloid leukemia and acute lymphocytic leukemia. Our study will enhance our understanding of putative risks of childhood leukemia associated with air toxics and will also assess differences in exposure assignment based on maternal address at delivery and address of the child at the time of diagnosis. Results will inform risk assessors and policy makers about combined effects arising from multiple chemical stressors, aid in the development of interventions to reduce risks of childhood leukemia associated with air pollution, and provide a framework for evaluating the potential for exposure misclassification due to residential mobility.