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，考虑到妇女一生中生活和工作的地方，特别强调她们在第一次分娩时的位置。本研究采用创新的数据链接方法和地理信息（GIS）技术，构建加州教师研究（CTS）成员中暴露于选定空气污染物的估计值，CTS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年时间跨度内的住宅和工作场所位置的配置文件，包括第一次出生前后的关键时间窗口，描述加州内CTS成员的移民历史;（2）描述与住宅相关的潜在空气污染暴露 和工作地点超过30年的时间，在经产妇女中，在第一次生育时;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，特别是针对第一次生育时的易感性目标窗口，并对已知的乳腺癌进行调整 风险因素和与地点相关的社会人口特征。研究人群将包括118，262名居住在加州且在入组研究时无乳腺癌病史的CTS队列成员。队列与预先存在的生命记录、商业可用地址信息和加州教育部文件的关联将用于构建30年时间跨度的居住和工作场所历史概况。此外，对于经产妇女，我们将使用这些联系来确定受试者在第一次活产时工作和生活的地方，因为这被认为是乳腺组织对环境损害的关键易感性的窗口。一个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联系起来。分析的目标化合物将包括那些在毒理学研究中显示会导致乳腺肿瘤的化合物和潜在的内分泌干扰物。通过与加州癌症登记处的联系，预计自CTS成立以来的15年内，将在CTS中确定约4 200例乳腺癌病例。将使用多变量考克斯模型（调整相关协变量），计算累积暴露量以及首次分娩前后与居住和工作地点相关的暴露量的乳腺癌风险估计值。在研究与环境空气污染物相关的潜在乳腺癌风险时，暴露几乎无处不在，这项研究提供了一个机会，以确定一种预防途径，可以大大减少这种疾病在未来妇女人口中的负担。

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.