Age-Related Patterns of Selected Protein-Altering Somatic Mutations and Overall Survival in Colorectal Cancer: A Retrospective Comparative Cohort Study

Background/Objectives: Early-onset colorectal cancer (EOCRC) is increasing in incidence and may exhibit adverse clinicopathological features, but whether selected somatic mutations differ by age remains uncertain. We compared clinicopathological characteristics, protein-altering somatic mutations, and overall survival between EOCRC and late-onset colorectal cancer (LOCRC) using TCGA-COAD/READ data. Methods: We conducted a retrospective comparative cohort study using publicly available clinicogenomic data. Patients were classified as EOCRC (<50 years) or LOCRC (≥50 years). Mutation-prevalence analyses were restricted to patients with evaluable somatic mutation data and corrected for multiple testing. Overall survival and exploratory age-by-mutation interactions were assessed using Kaplan-Meier and Cox regression. Results: Among 627 patients with available age-at-diagnosis data, 77 had EOCRC and 550 had LOCRC. Somatic mutation data were evaluable for 74 and 504 patients, respectively. EOCRC was associated with higher AJCC pathological stage (p = 0.021) and greater pathological nodal involvement (p = 0.007). Stage IV disease was associated with higher adjusted odds of EOCRC (adjusted OR, 2.64; 95% CI, 1.10-6.71; p = 0.033). No selected mutation-prevalence comparison remained statistically significant after false discovery rate correction. MSH2 mutation was nominally more frequent in EOCRC (8.1% vs. 2.8%; p = 0.032) but was nonsignificant after correction (q = 0.128). Age group was not associated with overall survival in the fully adjusted model (adjusted HR, 0.64; 95% CI, 0.33-1.25; p = 0.194). Conclusions: EOCRC was associated with higher pathological stage and greater nodal involvement in this TCGA cohort.