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

描述（由申请人提供）：本研究的目的是评估与暴露于环境空气污染相关的乳腺癌风险，考虑到女性一生中生活和工作的地点，特别强调她们第一胎出生时的地点。这项研究使用数据链接和地理信息 (GIS) 技术的创新方法来估算加州教师研究 (CTS) 成员对选定空气污染物的暴露程度，这是迄今为止专门为研究乳腺癌风险而组建的最大队列。具体目标是： (1.) 通过构建 30 年时间跨度内的居住和工作地点概况（包括第一胎出生前后的关键时间窗口）来描述 CTS 成员在加州的移民历史； (2.) 表征与住宅相关的潜在空气污染暴露 30 年期间的工作地点，以及对于已产妇女来说，在第一胎时的工作地点； (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，特别是针对第一胎出生前后的目标易感性窗口，并根据已知乳腺癌进行调整 与地点相关的风险因素和社会人口特征。研究人群将包括 118,262 名 CTS 队列成员，他们居住在加利福尼亚州，在进入研究时没有乳腺癌病史。该队列与预先存在的重要记录、商业地址信息和加州教育部文件的链接将用于构建 30 年时间跨度的居住和工作场所历史档案。此外，对于经产妇女，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，因为这被认为是乳腺组织对环境损害的严重易感性的一个窗口。地理信息系统将用于将住宅和工作地点与现有的空气质量数据库连接起来。用于分析的化合物将包括那些在毒理学研究中已被证明会导致乳腺肿瘤的化合物和潜在的内分泌干扰物。预计自 CTS 成立以来的 15 年内，通过与加州癌症登记处的联系，将发现大约 4,200 例乳腺癌病例。将使用多变量 Cox 模型计算累积暴露以及与第一胎出生前后居住和工作地点相关的乳腺癌风险估计，并调整相关协变量。在研究与环境空气污染物（其暴露几乎无处不在）相关的潜在乳腺癌风险时，这项研究提供了确定预防途径的机会，可以大大减轻未来女性群体中这种疾病的负担。

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.