The 10,000 Families Cohort: a new study to understand the environmental causes of cancer

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Abstract The 10,000 Families Study (10KFS) will be a new, family-based cohort study in Minnesota, the ‘Land of 10,000 Lakes’. Due to our high incidence rates of hematologic malignancy (leukemia, lymphoma, and myelodysplastic syndromes), we will focus our proposal on environmental exposures of concern that are possible hematologic carcinogens with limited evidence in humans as defined by the International Agency for Research on Cancer (IARC). This includes glyphosate, poly- and perfluoroalkyl substances (PFAS), and radon, all of which have well-described geographic variation in prevalence in the state of Minnesota. During the UG3 phase, we will evaluate innovative exposure assessment methodologies and recruit diverse participants into the 10KFS cohort. Exposure assessment will include residential history, ambient measures in air and water at current residence, as well as individual-level exposure assessed with silicone wearable bracelets, serum, hair, and urine. Participants will be recruited from targeted counties that maximize the exposure distribution to our three carcinogens of interest and include under-represented populations from rural and immigrant communities. We will measure clonal hematopoiesis of indeterminate potential (CHIP), a precursor to heme malignancy, and perturbations in immunity and epigenetics as our primary cancer-related outcomes in the UH3 phase. Our target is to recruit 8,750 participants from 4,000 households to participate using recruitment strategies that have been developed and pilot tested. Our central hypothesis is that PFAS, glyphosate and radon contribute to increased hematologic malignancy specifically, and cancer incidence broadly, in Minnesota. Cancer incidence will be determined via annual record linkage with the Minnesota Cancer Reporting System (MCRS) and the Virtual Pooled Registry Cancer Linkage System. The scientific aims in the UG3 phase will be to: 1) evaluate innovative exposure assessment methods for PFAS and glyphosate that can be easily implemented in a large scale study and 2) describe the exposure burden in under-represented immigrant populations. We will complete recruitment of the study population in the UH3 phase where the specific aims are to: 1) determine whether levels of radon, glyphosate, and PFAS are associated with increased prevalence of CHIP and 2) utilize epigenomics to test the hypotheses that radon, glyphosate and PFAS exposure are associated with immune dysregulation and epigenetic signatures. Our community engagement will be conducted in partnership with the non-profit research institute Hispanic Advocacy and Community Empowerment Through Research (HACER), the Minnesota Freemasons and Order of the Eastern Star and community educators from the Extension Center for Family Development. The results of this study will provide needed data to inform whether these agents are hematologic carcinogens, it will address documented disparities in exposure that occur within our state and provide a mechanism for community outreach and education concerning these exposures and any potential cancer link.