Abstract 7405: Temporal evolution of early signs and symptoms of early-onset colorectal cancer in diverse populations: Insights from the All of US Research Program

Abstract Introduction: The incidence of early-onset colorectal cancer (EOCRC, diagnosed before age 50) has risen sharply over the past three decades. Current screening guidelines are inadequate for detecting EOCRC in individuals under the recommended screening age, emphasizing the urgent need for identifying pre-diagnostic signs and symptoms and their temporal evolution patterns to inform early detection. Methods: A total of 347 incident EOCRC cases within the NIH All of Us Research Program (1991-2022) with ≥1 year of pre-diagnostic electronic health record (EHR) were matched with up to four controls. Signs and symptoms were classified as chronic (vs non-chronic) based on whether required ongoing medical care or impacted daily functioning for ≥12 months. Poisson regression models and dynamic network analyses were used to identify signs and symptoms from 1 year to 3 months before diagnosis and characterize their co-occurrence network within 2 years to diagnosis. Longitudinal trajectory analysis was used to examine the evolution of symptom intensity over 3-month sliding windows from 2 years to diagnosis. Results: From 1 year to 3 months pre-diagnosis, 16 non-chronic signs and symptoms were significantly associated with increased EOCRC risk, with the highest incidence rate ratios (IRRs) for blood in stool (IRR 12.9, 95% CI 4.4-38.1) and hemorrhage of rectum and anus (11.4, 5.0-26.0). Network analysis identified three symptom clusters centered on abdominal pain: (1) hemorrhage of the rectum and anus, which connects to blood in stool, acute pain, and anal/rectal conditions; (2) benign neoplasm of the colon; and (3) nausea and vomiting, back pain, syncope and collapse, and urinary tract infection, which interconnect. Clusters 1 and 2 co-occurred increasingly from 2 years to 3 months pre-diagnosis, with connections between clusters 1 and 3 emerging in the final 3 months. Longitudinal trajectory analysis demonstrated a steady increase in symptom intensity, accelerating 9 months before diagnosis, for abdominal pain, hemorrhage of rectum and anus, blood in stool, benign neoplasm of colon and anal and rectal conditions. Conclusion: Mapping symptom networks and their temporal evolution offers a promising path to enhance EOCRC detection. Integrating these insights into precision diagnostics can align with advanced prevention frameworks, improving outcomes for younger at-risk populations. Citation Format: Ruiyi Tian, Chongliang Luo, Xiaoyu Zong, Cassandra D. Fritz, Philip R. Payne, Yin Cao. Temporal evolution of early signs and symptoms of early-onset colorectal cancer in diverse populations: Insights from the All of US Research Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7405.