When the carcinogenic window opens before the screening window: the age-threshold blind spot in early-onset colorectal cancer.

Early-onset colorectal cancer (EOCRC) screening is constrained by a structural blind spot concealed by age-threshold-based eligibility. This limitation does not primarily reflect insufficient screening resources, but rather a fundamental temporal mismatch between screening logic and carcinogenic exposure. High-risk states may be established decades earlier through accumulated early-life "exposure memory," whereas screening triggered by chronological age can intervene only after risk has already been formed. Consequently, individuals younger than 45 years-the population with one of the fastest increases in EOCRC incidence-remain systematically overlooked even after the initiation age for average-risk screening has been lowered to 45 years. This article outlines two parallel pathways: the metabolic-inflammatory axis, including hyperinsulinemia, IGF-1 signaling, and chronic low-grade inflammation; and the gut microbiome axis, including microbial genotoxicity and mucosal immune dysregulation. We clarify how these pathways may encode risk early in life and jointly shift the carcinogenic window forward, making further reductions in age thresholds insufficient for timely identification of truly high-risk young individuals. Accordingly, we argue that EOCRC screening should move from "age-triggered detection" toward "risk-memory recognition." We propose three strategies stratified by clinical readiness: symptom-triggered colonoscopy triage as diagnostic evaluation rather than screening, earlier assessment of exposure memory, and microbiome-informed risk stratification as a research direction. These approaches may help identify high-risk individuals before the conventional screening age and reduce missed diagnoses and diagnostic delays.