BACKGROUND: Rates of early-onset colorectal cancer (eoCRC), defined as disease diagnosed at <
50 years of age, are increasing. The incidence and spectrum of somatic and pathogenic germline variants (PGV) in this population are not well understood. METHODS: This cross-sectional study leveraged Tempus' clinicogenomic database, including de-identified records of patients diagnosed with CRC between 2000-2022, to analyze and compare eoCRC and average-onset colorectal cancer (aoCRC, disease diagnosed ≥50 years of age) patients. The frequency and spectrum of somatic mutations and PGVs in patients with eoCRC and aoCRC were evaluated and compared. RESULTS: Among 11,006 participants in this study, 57% were male, 76% were white, and 80% had stage 4 disease. Within the total cohort, 2379 had eoCRC and 8627 had aoCRC. Among patients with eoCRC, 4.2% had a tumor with high microsatellite instability and/or deficient mismatch repair (MSI-H/dMMR) and 6.8% with aoCRC had an MSI-H/dMMR tumor ( CONCLUSIONS: Somatic and germline mutation profiles were similar for eoCRC and aoCRC patients and may not adequately explain differences in tumor behavior and age of disease onset.