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

美国许多社区因私营企业和政府管理而失败 保护当地环境，从而保护健康。该提案的目标是建立 MI-CARES： 密歇根癌症与环境研究 研究描述和量化已知和 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 空气污染和重金属等致癌物，但也关注不太特征的暴露，包括 全氟烷基物质和多氟烷基物质 (PFAS)、噪音以及个人护理产品中的化学物质 迫切需要评估致癌性。由于这些风险暴露的差异在地理区域上很常见， 社会经济地位、种族/民族和生活方式，需要进行研究以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) 是开展活动的理想地点 关于环境暴露和癌症风险的研究。密歇根人经历了一系列悲惨的事情 环境暴露包括动物饲料中多溴联苯 (PBB) 的污染 20 世纪 70 年代，弗林特供水系统出现铅污染，PFAS 含量达到所有州最高水平。的 底特律都会区的“三城”地区是一个以黑人和西班牙裔为主的社区，也是美国污染最严重的地区 密歇根州和整个美国的高层。密歇根州的这些曝光是深刻的，并且有着悠久的历史 社区参与使 MI-CARES 变得可行。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 MI-CARES，一个种族/民族多元化的组织 居住在密歇根州环境不公正热点地区的 100,000 名 25-44 岁无癌症男性和女性队列： 底特律都会区、弗林特、大急流城、卡拉马祖、兰辛和萨吉诺。我们将平等招聘 黑人、西班牙裔、中东和北非 (MENA) 以及白人参与者的数量；除后者之外的所有 在环境和癌症研究中代表性不足。问卷、社区级数据和出生 将使用生命历程方法收集所有参与者的记录，以在关键窗口期间捕获数据 的易感性。数据收集将包括有关个人社会人口统计、居住历史、 健康和生活方式。通过问卷调查确定终生接触环境污染物的情况， 基于住宅邻近性的措施或模型。此外，生物样本（血斑和唾液）将被 收集所有参与者。在 MI-CARES 内，我们将组建一个增强测量队列（n=1,000 名癌症患者） 免费队列成员）和嵌套病例对照样本（n=250 例癌症病例和 250 例匹配的无癌症病例） 队列对照）其中基于实验室的综合暴露和中间癌症生物标志物 将进行评估，包括 PFAS、金属、非目标代谢组学、DNA 甲基化和 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.