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

描述(申请人提供)：儿童白血病，最常见的儿科癌症，其病因尚不清楚。苯是一种已知的成人白血病原，环境中暴露于这种致癌物被假设在儿童白血病的发生中起作用，其他空气有毒物质也可能与此有关。这项调查将是迄今为止进行的最大规模的研究，以评估暴露在空气中对儿童早期急性髓细胞白血病(AML)和急性淋巴细胞白血病(ALL)风险的影响。此外，应用程序的方法学部分将严格评估从出生时到确诊时因居住地变化而导致的暴露分配的差异。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相关的癌症风险，因为该州拥有广泛的道路交通，以及该州运营的石化设施和燃煤发电厂的数量。在健康、社会和经济差距方面，该州在全国的排名也很低。将采用病例对照研究设计，对个人和社区水平的混杂因素进行控制。0-4岁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。将使用美国环保局全国范围空气有毒物质评估中对普查地区环境空气中苯、1，3-丁二烯和多环芳烃(PAHs)水平的模拟估计来评估居民暴露于空气有毒物质的情况。第一个目标将是利用模拟的人口普查地区苯、1，3-丁二烯和多环芳烃水平估计来评估急性淋巴细胞白血病和急性髓细胞白血病的风险与环境空气污染之间的联系。还将评估这些空气污染物的综合影响。由于对环境空气污染和儿科后果的研究往往依赖出生证明中提供的分娩时母亲的地址来对接触进行分类，第二个目标将根据出生时的母亲地址和诊断时的儿童地址评估暴露分配的差异。这项拟议的研究具有重要意义，因为它将(1)加强我们对与空气毒物相关的儿童白血病可能风险的理解，(2)帮助流行病学家在未来对儿童白血病和其他儿科结果的研究中考虑从出生到诊断的居住地流动性的影响。结果将使风险评估员和政策制定者了解多种化学应激源产生的综合影响，帮助制定干预措施，以降低与空气污染相关的儿童白血病风险，并提供一个框架，评估由于居住流动性而导致暴露于错误分类的可能性。 公共卫生相关性：这项调查将是迄今为止进行的最大规模的研究，以评估接触空气有毒物质对儿童早期急性髓细胞白血病和急性淋巴细胞白血病风险的影响。我们的研究将加强我们对与空气有毒物质有关的儿童白血病可能风险的理解，并将评估基于母亲分娩时地址和诊断时儿童地址的暴露分配的差异。结果将使风险评估员和政策制定者了解多种化学应激源产生的综合影响，帮助制定干预措施，以降低与空气污染相关的儿童白血病风险，并提供一个框架，评估由于居住流动性而导致暴露于错误分类的可能性。

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.