Air Pollution and Childhood Cancers in California

描述（由申请人提供）：儿童癌症的病因尚不清楚，因此预防的机会很少。与交通相关的空气污染是一种可能的人类致癌物，其中苯、1,3-丁二烯和多环芳烃 (PAH) 等污染成分是人类癌症的确定原因。有证据表明，胎儿比成人更容易受到多种污染物的影响，包括多环芳烃和颗粒物。然而，迄今为止，关于空气污染和儿童癌症的文献很少，几乎所有研究都利用了生态设计或空气质量的简单替代指标，而不是依赖于对标准空气污染物或特定空气毒物的监测，或利用复杂的暴露模型。此外，儿童癌症的罕见性需要小样本量，很少有研究有足够的能力报告特定儿童癌症亚型的风险。在拟议的研究中，我们希望利用对标准空气污染物的大规模空气监测和基于社区的空气毒物监测数据的独特资源来检查加州儿童的癌症风险。符合资格的受试者将包括加州癌症登记处 d5 岁的儿童（1988-2007 年，N=12042），以及从加州出生名单中随机选择的每个病例 10 名对照。我们的具体目标是：(1) 使用 4 个指标来估计产前和儿童早期接触空气污染的情况：来自政府运营的监测站的现有测量数据；通过 CALINE4 空气扩散模型估算的 NOX 和 PM2.5；距离加权交通密度，这将有助于将结果与以前的研究进行比较；使用现有社区空气监测站的测量数据确定特定空气有毒物质（苯、1,3 丁二烯、多环芳烃）； (2) 检验与交通相关的空气污染会增加儿童癌症风险的假设； (3) 检验一般背景空气污染会增加癌症风险的假设； (4) 检验某些空气毒物会增加儿童癌症风险的假设，特别关注与脑癌和造血系统癌症相关的多环芳烃；苯与造血系统癌症；和1,3丁二烯与造血系统癌症。上述污染物的风险将根据出生证明上的地理编码居住地址产生。拟议的研究将是迄今为止最大规模的研究与空气污染相关的癌症风险的研究，并将利用个人层面的、完善的和经过验证的车辆尾气相关污染浓度测量方法。重要的是，我们希望这些发现能够加深我们对机动车空气毒物是否是先前研究中观察到的儿童癌症与空气污染物之间关联的主要驱动因素的理解。如果拟议的研究能够查明与出生结果更相关的特定毒素，那么未来使用个人和生物监测的研究将能够针对这些化合物。 公共健康相关性：癌症是婴儿期至 15 岁儿童死亡的第二大原因，预计 2008 年美国将有 10,730 例新病例。儿童癌症的病因尚未得到很好的阐明。拟议的研究将检查围产期和生命早期接触空气污染的情况，并检验与后期癌症发展相关的假设。

DESCRIPTION (provided by applicant): The etiology of childhood cancers is not well understood, and as such, the opportunities for prevention are few. Traffic-related air pollution is a possible human carcinogen, and constituents of are pollution such as benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) are established causes of human cancers. Evidence suggests that the fetus is more susceptible than the adult to a number of pollutants including PAHs and particulate matter. To date, however, there is only a small literature on air pollution and childhood cancers, and nearly all studies have utilized ecologic designs or simple proxies of air quality rather than relying on monitoring of criteria air pollutants or specific air toxics, or by utilizing sophisticated exposure models. Further, the rarity of childhood cancers have necessitated small sample sizes with few studies having adequate power to report risks for specific childhood cancer subtypes. In the proposed study, we wish to capitalize on the availability of widescale air monitoring of criteria air pollutants and the unique resource of community-based air toxics monitoring data to examine cancer risk among California children. Eligible subjects will include children age d5 in the California Cancer Registry (1988-2007, N=12042) and 10 controls per case selected at random from California birthrolls. Our specific aims are: (1) to estimate prenatal and early childhood exposures to air pollution using 4 metrics: existing measurement data from government operated monitoring stations; NOX and PM2.5 as estimated by CALINE4 air dispersion modeling; distance-weighted traffic density, which will be useful to compare results to previous studies; and specific air toxics (benzene, 1,3 butadiene, PAHs) using measurement data from existing community-based air monitoring stations; (2) to test the hypothesis that traffic-related air pollution increases risk of childhood cancer; (3) to test the hypothesis that general background air pollution increases cancer risk; (4) to test the hypothesis that certain air toxics increase risk of childhood cancers, with a particular focus on PAHs with brain and hematopoietic cancers; benzene with hematopoietic cancers; and 1,3 butadiene with hematopoietic cancers. Risks for the above pollutants will be generated based upon geocoded residential address, taken from birth certificates. The proposed study will be the largest to date to examine the cancer risks associated with air pollution and will utilize individual-level, refined and validated measures of vehicle exhaust related pollution concentrations. Importantly, we expect the findings to enhance our understanding of whether motor vehicle air toxics are the primary drivers of associations between childhood cancers and air pollutants observed in previous studies. If the proposed research is able to pinpoint specific toxins of greater relevance to birth outcomes, future research using personal and biomonitoring would be able to target these compounds. PUBLIC HEALTH RELEVANCE: Cancers are the second leading cause of death among children between infancy and age 15, with 10,730 new cases expected in the US in 2008. The etiology of childhood cancers is not well elucidated. The proposed study will examine perinatal and early life exposure to air pollution and test hypotheses of associations with later cancer development.