Pathways to Prevention: Exploring Social Determinants of Health in Early Onset Colorectal Cancer - PROJECT ABSTRACT Background: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before age 50, has been on the rise in the United States, with age-adjusted incidence increasing from 5.9 cases per 100,000 individuals in 2000 to 8.4 cases in 2017, and mortality rising by approximately 1.3% annually from 2008 to 2017. Factors contributing to EOCRC include lifestyle factors, chronic diseases, family history, and multi-level social determinants of health (SDoH), which encompass conditions such as economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social and community context. Notably, Black/African American people and individuals in rural communities face greater SDoH burdens and significant inequities in EOCRC outcomes. Our preliminary research shows that EOCRC mortality hotspots are more prevalent in southern U.S. counties with higher proportions of Black residents. However, lack of research including integration of comprehensive and multifaceted SDoH factors into evaluation of EOCRC disparities. Objective/Hypothesis: The primary objective of this study is to evaluate the impact of various SDoH on EOCRC diagnosis and delays in the first course of treatment and survival, focusing on geographically and racially underserved populations in Kentucky and Georgia. We hypothesize that SDoH measures related to economic stability, education, healthcare access, neighborhood environment, and social context significantly influence EOCRC outcomes, with a greater impact on younger populations (under 50 years). Specific Aims: The study will utilize an epidemiologic approach analyzing secondary data within two specific aims. Aim 1: To elucidate the relationship between standardized measures of SDoH and CRC diagnosis, and whether these associations are modified by age at diagnosis, sex, and race/ethnicity. We will analyze cohort data from the All of Us research program (Nov 2021-2024) to examine the association between SDoH and CRC diagnosis, stratified by different ages at diagnosis (<50 and ≥50 years; <45 and ≥45 years), sex, and race/ethnicity. Aim 2: To examine the relationship between area-level SDoH and delays in treatment and survival for CRC in Georgia and Kentucky, and whether these associations are modified by age at diagnosis. We will use retrospective cohort data from the 2014-2024 Kentucky and Georgia cancer registries. Cox proportional hazards models will assess the association between area-level SDoH (defined by the social vulnerability index [SVI]) and delays in the first course of treatment (time between diagnosis and treatment start) and survival, stratified by age at diagnosis (<50 and ≥50 years; <45 and ≥45 years). Cancer Relevance: This research addresses critical gaps in understanding how various SDoH impact EOCRC outcomes among younger populations in underserved communities. Findings will inform public health initiatives and policies to improve equitable access to cancer diagnosis and treatment resources for young adults in Kentucky and Georgia, ultimately contributing to EOCRC mortality reduction and better health outcomes in these populations/communities.