Where were you then? New insights into breast cancer and the environment (PQ2)

描述(申请人提供)：这项研究的目标是评估与暴露在环境空气污染中有关的乳腺癌风险，考虑到妇女一生中生活和工作的地方，特别强调她们第一次出生时在哪里。这项研究使用数据链接和地理信息(GIS)技术的创新方法，在加州教师研究(CTS)的成员中建立了对选定空气污染物暴露的估计，这是有史以来专门研究乳腺癌风险的最大队列。具体目标是：(1)通过构建30年时间跨度的住宅和工作地点的概况，包括第一次出生前后的关键时间窗口，来描述加州社区服务成员的迁徙历史；确定与住宅相关的潜在空气污染暴露的特征 和工作地点，在30年内，对于临产妇女来说，是在第一次分娩时；和(3)估计30年内与住宅和工作场所相关的选定空气污染物相关的乳腺癌风险，特别是第一次生育前后的目标易感窗口，调整已知的乳腺癌 与地点相关的危险因素和社会人口学特征。研究人群将由118,262名CTS队列成员组成，他们居住在加利福尼亚州，在进入研究时没有乳腺癌史。该队列与先前存在的重要记录、商业上可获得的地址信息和加州教育部文件的联系将被用于构建30年时间跨度的住宅和工作场所历史档案。此外，对于临产妇女，我们将利用这些联系来确定受试者在第一次活产前后的工作和生活地点，因为这被认为是乳房组织对环境侮辱的关键易感性的窗口。将使用地理信息系统将住宅和工作地点与现有的空气质量数据库联系起来。作为分析目标的化合物将包括那些在毒理学研究中被证明会导致乳腺肿瘤的化合物和潜在的内分泌干扰物。预计在CTS成立以来的15年里，通过与加州癌症登记中心的联系，大约有4200例乳腺癌病例将在CTS中被发现。乳腺癌风险估计将使用多变量Cox模型计算累积暴露以及与第一次出生时居住和工作地点相关的风险，并对相关协变量进行调整。在研究与环境空气污染物相关的潜在乳腺癌风险时，这项研究提供了一个机会，找出一种预防的途径，可以在未来的女性群体中大幅减轻这种疾病的负担。

DESCRIPTION (provided by applicant): The objective of this study is to estimate the risk of breast cancer associated with exposures to ambient air pollution, taking into account where women have lived and worked throughout their lives, with a special emphasis on where they were at the time of their first birth. This study uses innovative methods of data linkage and geographic information (GIS) technologies to construct estimates of exposure to selected air contaminants among members of the California Teachers Study (CTS), the largest cohort ever assembled specifically to study breast cancer risk. The specific aims are to: (1.) Characterize the migration history of CTS members within California by constructing profiles of residential and workplace locations over a 30-year time span, including for the critical window of time around first birth; (2.) Characterize potential air pollution exposures associated with residential and workplace location over a 30-year period and, among parous women, at the time of first birth; and (3.) Estimate the risk of breast cancer associated with selected air contaminants associated with residential and workplace locations over a 30-year period, especially for the targeted window of susceptibility around the time of first birth, adjusting for known breast cancer risk factors and sociodemographic characteristics associated with place. The study population will consist of the 118,262 CTS cohort members who were residing in California and did not have a history of breast cancer when they entered the study. Linkage of the cohort to pre-existing vital records, commercially-available address information, and California Department of Education files will be used to construct residential and workplace history profiles for a 30-year time span. Additionally, for parous women, we will use these linkages to identify where subjects worked and lived at the time around their first live birth, as this is thought to be a window of critical susceptibility of breast tissue to environmental insults. A GIS will be used to link the residential and workplace locations to existing air quality databases. Compounds targeted for analysis will include those that have been shown to cause mammary gland tumors in toxicological studies and potential endocrine disruptors. It is anticipated that approximately 4,200 cases of breast cancer will be identified in the CTS in the 15 years since its inception, through linkage to the California Cancer Registry. Breast cancer risk estimates will be calculated for both cumulative exposures and those associated with residential and workplace locations around time of first birth using multivariable Cox models, adjusting for relevant covariates. In studying potential breast cancer risks associated with ambient air pollutants, for which exposures are nearly ubiquitous, this study offers the opportunity to identify an avenue for prevention that could substantially reduce the burden of this disease among future populations of women.