PROJECT 2: WATER FOR HEALTH: PROJECT SUMMARY For decades, the Strong Heart Study (SHS) has collaborated with American Indian/Alaska Native (AI/AN) communities in the Northern Plains, Southern Plains, and Southwest to improve cardiovascular health through various multi-level interventions and state-of-the-art epidemiologic research. AI/AN communities experience significantly elevated drinking water arsenic and uranium exposures in both private wells and regulated public drinking water systems. However, the contribution of these modifiable drinking water exposures to AI/AN disparities in arsenic and uranium-associated cancer incidence mortality remains poorly characterized. Arsenic- and uranium- associated cancers are of increasing concern for SHS communities and AI/AN communities nationwide, as AI/AN communities experience increasing disparities in incidence for these cancers (lung, bladder, kidney, pancreas, prostate). The objective of the proposed project is to support multi- level interventions to reduce water arsenic and uranium for AI/AN communities, with the ultimate goal of reducing arsenic and uranium associated cancers for AI/AN communities. The proposed project is grounded in a conceptual model linking local social-ecological frameworks for health disparities and disparities in water arsenic exposures with Indigenous frameworks weaving mainstream science with Indigenous Knowledge. In Aim 1, we will comprehensively characterize exposure to arsenic and uranium in unregulated well and public water systems across all SHS communities and disseminate individualized dashboards to tribal communities. In addition to leveraging available resources that have not been compiled for stakeholder use, we will extend process-based models for estimating groundwater arsenic and geospatial models of arsenic/uranium in regulated public water to all SHS communities. In Aim 2, we will conduct state-of-the-art epidemiologic analyses to evaluate the association between water arsenic and uranium with incident and fatal cancers of the lung, bladder, kidney, pancreas, and prostate in the SHS, with a focus on estimating the impacts of potential interventions on cancer rates. These data are critical because AI/AN populations remain unrepresented in epidemiologic science driving federal drinking water standards. In Aim 3, we will conduct formative research with eight SHS communities and comprehensively review successful multi-level intervention plans with community priorities, needs, strengths, and challenges, with the ultimate goal of supporting communities to develop culturally relevant and individualized intervention plans to reduce water arsenic and uranium. Our proposal brings together a multi-disciplinary, multi-site team, and leverages decades of collaboration and community engagement with SHS communities across all three SHS study sites. The proposed study responds directly to the NIMHD-identified need for community-driven prevention strategies to reduce the i...