Molecular Heterogeneity in Early-Onset Colorectal Cancer: Pathway-Specific Insights in High-Risk Populations

This study highlights the substantial molecular heterogeneity present in EOCRC, particularly among high-risk populations. The H/L EOCRC patients exhibited distinct genetic alterations, with a higher prevalence of CBL, NF1, RNF43, BMPR1A, and MAPK3 mutations compared to their NHW counterparts. Additionally, RTK/RAS pathway alterations were less frequent in EOCRC than in LOCRC. Despite these molecular differences, pathway alterations did not significantly impact survival outcomes in the H/L EOCRC patients. However, in the NHW EOCRC patients, the presence of WNT pathway alterations was associated with improved survival. These findings emphasize the necessity for further research to clarify the molecular mechanisms driving EOCRC disparities in high-risk populations and to inform precision medicine strategies for underrepresented groups.