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

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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.