ABSTRACT. The broad, long-term objectives of this K01 project are to improve the health of Apache American Indians through a study that examines the association between cancer (CA) outcomes and Arsenic (As), co- metals, and nitrate on the San Carlos Apache (SCA) reservation in Arizona. The study setting has an extensive history of hard rock mining since the early 1900s when uranium (U), copper, silver, and asbestos were extracted. Anthropogenic causes and naturally occurring elements can cause movement of As and co-metals into the environment and may result in adverse health effects. Arsenic is a known carcinogen and is associated with diabetes, adverse reproductive outcomes, and cardiovascular disease. A main goal of this pilot study is to develop and implement an exposure assessment tool (EAT) to study cancers and to use in the future to examine the association between exposures and multiple adverse health outcomes. The specific aims are to: 1) characterize historical water data by time and recorded As, Cd, Pb, U, and nitrate concentration levels from 1981-2021, 2) examine the association between chronically elevated As, Cd, Pb, U, and nitrate in water and CA outcomes (bladder, kidney, prostate, lung, breast, and skin), 3) analyze and apply a Geographic Information System (GIS) model to map high-risk (As, Cd, Pb, U, nitrate) areas based on this EAT, and 4) provide study findings to tribal members and leaders. A retrospective pair matched case-control (N = 160) design will be employed. Decades of As, Cd, Pb, U, and nitrates concentration levels recorded by the US Environmental Protection Agency (EPA), tribal EPA, and US Geological Survey from areas known to have elevated As, co-metal and nitrate concentration levels will be collected. Local tribal health/Indian Health Service (IHS) records will be examined for CA diagnoses and mortality (using ICD codes) reported by the IHS, tribal health, private health records, state CA registries, and mortality records of the past 10 years. Study controls will be selected from SCA enrollment data and matched to cases by sex and age. Odds Ratios will be reported using logistic regression to determine associations between exposure risk and outcomes. A dose response between chronic As, Cd, Pb, U, and nitrate water ingestion and reported cancers are anticipated. This is the first local study to retrospectively examine water contaminant levels in relation to multiple CA outcomes. The data will form the foundation for an R01 intervention study to educate, screen, and identify risks for adverse health outcomes among residents. Findings will be disseminated to tribal members and leaders, healthcare facilities, and the general population. This study has the potential to augment prevention efforts, intervention, education, monitoring/surveillance, and can support policy development and legislation. The project will reach a nationally underserved population in the biomedical, social, behavioral, and clinical sciences and is in alignment with training diverse scientists in fields per the NCI grant purpose and mission. The study addresses CA disparities in an underserved community while advancing scientific knowledge.

PROJECT NARRATIVE A retrospective case-control pilot study examines the association between chronic arsenic, cadmium, lead, uranium and nitrate in water and cancer outcomes in an American Indian community. The goal of this pilot project is to develop and implement an exposure assessment tool to use now and in the future to examine the association between exposures and a range of adverse health outcomes. This study has the potential to augment prevention efforts, intervention, education, monitoring, support policy development and legislation, and address longstanding cancer disparities and improve outcomes.