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， 保护当地的环境和健康。该提案的目标是建立MI-CARES： 密歇根州癌症和环境研究的研究，以描述和量化的影响， 新的环境暴露对癌症风险的影响。通过MI-CARES，我们将检查完善的环境 致癌物，如空气污染和重金属，但也侧重于不太特征的暴露， 全氟烷基和多氟烷基物质（PFAS）、噪音和个人护理产品中的化学物质， 迫切需要评估致癌性。由于各地理区域在这些风险方面的差异很普遍， 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如何影响 环境与癌症风险之间的关系。密歇根州（MI）是开展 研究环境暴露和癌症风险。美国人经历了一系列悲惨的 环境暴露，从受污染的动物饲料中的多溴联苯（PBBs）， 20世纪70年代，弗林特的供水铅污染，和最高的已知PFAS水平的任何国家。的 底特律大都会的“三城”地区，主要是黑人和西班牙裔社区，是美国污染最严重的地区。 密歇根州和高排名在整个美国这些风险敞口在MI是深刻的和强大的历史， 社区参与使MI-CARES可行。在这个项目中，我们假设环境 暴露会影响炎症、细胞衰老、表观遗传调节和免疫功能， 癌症风险。为了研究这一假设，我们建议建立MI-CARES，一个种族/民族多样化的 100，000名年龄在25-44岁的无癌症男性和女性，居住在密歇根州的环境不公正热点地区： 底特律都会区、弗林特、大急流城、卡拉马祖、兰辛和萨吉诺。我们将招募平等的 黑人、西班牙裔、中东和北非（MENA）以及白色参与者的数量;除后者外， 在环境和癌症研究中的代表性不足。问卷调查、社区一级数据和出生 将使用生命过程方法收集所有参与者的记录，以在关键窗口期间获取数据 敏感性。数据收集将包括个人社会人口统计学信息，居住历史， 健康和生活方式。将通过问卷调查确定终生接触环境污染物的情况， 基于住宅邻近度的措施或模型。此外，生物标本（血斑和唾液）将 收集所有参与者。在MI-CARES中，我们将形成一个增强的测量队列（n= 1，000名癌症患者， 免费队列成员）和巢式病例对照样本（n=250例癌症病例和250例匹配的无癌症 队列对照），其中基于实验室的全面暴露和中间癌症生物标志物 评估将进行，包括PFAS，金属，非靶向代谢组学，DNA甲基化， 炎症生物标志物。

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.