MI-CARES: The Michigan Cancer and Research on the Environment Study

美国各地的许多社区都因私营企业和政府的管理而失败 保护当地的环境，从而保护他们的健康。这项提议的目标是建立MI-CARE： 密歇根州癌症和环境研究描述和量化已知和 关于癌症风险的新的环境暴露。通过MI-CARE，我们将检查成熟的环境 致癌物质，如空气污染和重金属，但也关注不太典型的暴露，包括 个人护理产品中的全氟烷基物质和多氟烷基物质(PFAS)、噪音和化学品 迫切需要评估致癌性。由于这些暴露的差异在地理区域是常见的， 社会经济地位、种族/民族和生活方式，需要研究来了解这些因素是如何影响的 环境与癌症风险之间的关系。密歇根州(密歇根州)是一个理想的实施地点 环境暴露与癌症风险的研究。密歇根州人经历了一系列悲惨的 环境暴露范围从受污染的动物饲料中的多溴联苯(PBBS) 20世纪70年代，弗林特供水的铅污染，以及已知的任何州中最高的全氟辛烷磺酸水平。这个 底特律大都会的“三城区”是以黑人和西班牙裔为主的社区，是美国污染最严重的地区 密歇根州和整个美国排名很高。这些在密歇根州的暴露是深刻的和强大的历史 社区参与使MI-CARE成为可能。在这个项目中，我们假设环境 暴露会影响炎症、细胞老化、表观遗传调节和免疫功能，最终增加 癌症风险。为了研究这一假设，我们建议建立一个种族/民族多元化的MI-CARE 居住在密歇根州环境不公正热点地区的10万名年龄在25-44岁之间的无癌男性和女性： 底特律大都市区、弗林特、大急流城、卡拉马祖、兰辛和萨吉诺。我们将招聘同等数量的员工 黑人、西班牙裔、中东和北非(中东和北非)和白人参与者的人数；除后者外 在环境和癌症研究中的代表性不足。问卷、社区层面的数据和出生 将使用生命周期方法收集所有参与者的记录，以在关键窗口期间捕获数据 易感性。数据收集将包括个人社会人口统计信息、居住历史、 健康和生活方式。终身接触环境污染物将通过问卷调查确定， 基于住宅邻近度的衡量标准或模型。此外，生物制品(血斑和唾液)将 收集了所有参与者的信息。在MI-CARE内，我们将形成一个增强的测量队列(n=1,000个癌症- 自由队列成员)和嵌套病例对照样本(n=250例癌症病例和250例匹配的非癌症病例 队列对照)，在这些人中，全面的基于实验室的暴露和中间癌症生物标记物 将进行评估，包括全氟辛烷磺酸、金属、非靶向代谢组学、DNA甲基化和 炎症生物标记物。

Many communities around the U.S. have been failed by private enterprise and governmental stewardship in protecting their local environments and thus health. The goal of this proposal is to establish MI-CARES: The Michigan Cancer and Research on the Environment Study to describe and quantify the impact of known and novel environmental exposures on cancer risk. With MI-CARES we will examine well-established environmental carcinogens such as air pollution and heavy metals, but also focus on less characterized exposures including per- and polyfluoroalkyl substances (PFAS), noise, and chemicals in personal care products for which there are urgent needs to assess carcinogenicity. As disparities in these exposures are common by geographic region, socioeconomic status, race/ethnicity, and lifestyle, research is required to understand how these factors impact the relationships between the environment and cancer risk. Michigan (MI) is an ideal location to carry out research on environmental exposures and cancer risk. Michiganders have experienced a tragic suite of environmental exposures ranging from contaminated animal feed with polybrominated biphenyls (PBBs) in the 1970s, to the lead contamination of Flint’s water supply, and the highest known PFAS levels of any state. The “Tri-Cities” area of metro Detroit, a predominantly Black and Hispanic community, is the most polluted region in Michigan and high-ranking in the entire U.S. These exposures in MI are profound and the strong history of community engagement makes MI-CARES feasible. In this project, we hypothesize that environmental exposures impact inflammation, cellular aging, epigenetic regulation, and immune function to ultimately increase cancer risk. To investigate this hypothesis, we propose to establish MI-CARES, a racially/ethnically diverse cohort of 100,000 cancer-free men and women aged 25-44 residing in environmental injustice hotspots in MI: the Detroit metropolitan area, Flint, Grand Rapids, Kalamazoo, Lansing, and Saginaw. We will recruit equal numbers of Black, Hispanic, Middle Eastern and North African (MENA), and White participants; all but the latter are underrepresented in environmental and cancer research. Questionnaire, community-level data, and birth records will be collected for all participants using a life course approach to capture data during critical windows of susceptibility. Data collection will include information on individual sociodemographics, residential histories, health, and lifestyle. Lifetime exposures to environmental pollutants will be ascertained through questionnaire, residential proximity-based measures or models. In addition, biospecimens (blood spots and saliva) will be collected on all participants. Within MI-CARES, we will form an enhanced measurement cohort (n=1,000 cancer- free cohort members) and a nested case-control sample (n=250 cancer cases and 250 matched cancer-free cohort controls) in whom a comprehensive laboratory-based exposure and intermediate cancer biomarker assessment will be conducted, including PFAS, metals, untargeted metabolomics, DNA methylation, and inflammation biomarkers.