Justin Moore Pilot Scope: Translational Research on Associations between PFAS and Colorectal Cancer Etiology (TRACE) Study

PROJECT ABSTRACT Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States, with persistent poorer outcomes in rural and Appalachian populations. Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, persistent, and bioaccumulative environmental contaminants detected in water, soil, and human blood. PFAS exposure has been linked to chronic inflammation, immune dysregulation, and metabolic disruption, key pathways in colorectal carcinogenesis, yet epidemiologic evidence linking PFAS to CRC outcomes remains limited. No prior studies have integrated biomarker-based PFAS exposure with cancer registry and geospatial environmental data to examine CRC outcomes. Objective/Hypothesis: The objective of the Translational Research on Associations between PFAS and Colorectal Cancer Etiology (TRACE) study is to generate first-of-its-kind, multilevel evidence on PFAS exposure and colorectal cancer outcomes. We hypothesize that higher serum PFAS concentrations are associated with increased cancer-specific and CRC-specific mortality, and that CRC patients in Kentucky will exhibit elevated PFAS burden, particularly in rural/Appalachian and environmentally exposed communities. Specific Aims: This innovative study integrates national and state-level data across two aims. In Aim 1 we will examine associations between serum PFAS exposure and cancer-specific mortality using National Health and Examination Survey (NHANES)- National Death Index (NDI) restricted linked mortality data (2003–2018; follow-up through 2022), including exploratory analyses on effect modification by race/ethnicity and rurality. In Aim 2 we gather preliminary evidence on the presence of PFAS exposure in 30 blood serum samples from CRC patients within the Markey Cancer Center, and whether patient PFAS levels are higher than national estimates, and differ by rural/Appalachian status. Cancer Relevance: This project provides a highly innovative integration of available NHANES biomarker with mortality data, and Kentucky cancer registry to evaluate PFAS as a modifiable environmental risk factor for CRC outcomes. Findings will generate actionable evidence on environmental drivers of CRC outcomes and inform targeted prevention strategies to reduce CRC burden in high-risk populations.