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科癌症，其病因仍不清楚。苯是一种已知的成人白血病原，环境空气中暴露于这种致癌物质被假设在儿童白血病的发病率中发挥作用，其他空气毒物也可能涉及。这项调查将代表迄今为止进行的最大规模的研究，以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，应用程序的方法学部分将严格评估由于出生至诊断期间居住地的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领域，以评估与暴露于空气有毒物质相关的癌症风险，因为其广泛的道路交通以及在该州运营的石化设施和燃煤电厂的数量。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，控制个体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确定，对照组将从德克萨斯州出生证明记录中取样。将使用美国环保署全国范围空气毒性评估中的苯、1，3-丁二烯和多环芳烃（PAH）普查区环境空气水平的模型估计值，评估居民暴露于空气毒性的情况。第一个目标将是评估急性淋巴细胞白血病和急性髓细胞白血病的风险和环境空气污染之间的关系，使用苯，1，3-丁二烯和多环芳烃的模拟人口普查水平估计。这些空气污染物的综合影响也将得到评估。由于环境空气污染和儿科结果的研究往往依赖于母亲在分娩时的地址，从出生证明中可以对暴露进行分类，第二个目标将根据母亲在出生时的地址和孩子在诊断时的地址评估暴露分配的差异。这项研究的意义在于：（1）提高我们对与空气毒物相关的儿童白血病的推定风险的理解;（2）帮助流行病学家在未来的儿童白血病和其他儿科结局研究中考虑从出生到诊断的居住流动性的影响。研究结果将告知风险评估人员和政策制定者有关多种化学应激源产生的综合影响，帮助制定干预措施以减少与空气污染相关的儿童白血病风险，并提供一个框架，用于评估由于居住流动性而导致暴露错误分类的可能性。 公共卫生相关性：这项调查将代表迄今为止进行的最大规模的研究，以评估空气毒性暴露对儿童早期急性髓性白血病和急性淋巴细胞白血病风险的影响。我们的研究将提高我们对与空气有毒物质相关的儿童白血病的推定风险的理解，并将评估基于分娩时母亲地址和诊断时儿童地址的暴露分配差异。研究结果将告知风险评估人员和政策制定者有关多种化学应激源产生的综合影响，帮助制定干预措施以减少与空气污染相关的儿童白血病风险，并提供一个框架，用于评估由于居住流动性而导致暴露错误分类的可能性。

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.