694 Comparison of the Molecular and Genetic Features of Early and Late Onset Colorectal Cancer

Document Type

Conference Proceeding

Publication Date

3-23-2026

Publication Title

Lab Invest

Keywords

adult, aged, colorectal cancer, conference abstract, controlled study, female, genetic variability, histology, histopathology, human, human tissue, immunofluorescence, immunohistochemistry, inflammatory bowel disease, major clinical study, male, neoplastic cell transformation, protein analysis, retrospective study

Abstract

Disclosures: Burak Muratoglu: None; Pegah Dejban: None; Imeelda Altone: None; Muhammad Bilal: None; Beena Ahsan: None Background: Colorectal cancer (CRC) is increasingly being diagnosed in younger individuals; however, whether the molecular and histopathologic landscape of early-onset disease differs from CRC diagnosed in older patients remains incompletely defined. This study aimed to compare the molecular and genetic features of CRC diagnosed in younger versus older patients. Design: We performed a retrospective study of patients diagnosed with CRC between 2015 and 2024. Patients were stratified into 2 groups: <50 years and ≥50 years. Clinical records, histology results, immunohistochemical MMR protein analyses, and disease-associated genetic variant testing data were collected. Comparative descriptive statistics were used to explore differences between groups and describe the mutation burden of early-onset and late-onset CRC Results: Of 300 patients with CRC patients (150 <50 years; 150 ≥50 years), a significantly smaller proportion of younger patients than older patients died within the study period (20% vs 31%; p=.025), but a higher proportion had inflammatory bowel disease–associated CRC (7% vs 1%; p=.018). Most tumors in both groups were MMR-proficient (93% vs 92%; p=.658). A total of 104 patients had sequence variant analysis performed: 76 younger and 28 older patients. Half of these patients (n=52) had no genetic variants identified; however, the number of mutated genes identified was associated with age group (p=.002), with a higher proportion of younger patients having no mutated genes (61% vs 21%). Also, there were 2 younger and no older patients who had 6 or more mutated genes identified, while a greater proportion of older patients had 1 single mutated gene (68% vs 24%). Of the 17 specific genetic variants evaluated, KRAS was the most commonly identified in 18 (17.3%) patients, including in 10/76 (13.2%) younger and 8/28 (28.6%) older individuals. Interestingly, 5 of the 6 BRAF variants, 3 of the 4 NRAS variants, and all 4 MLH1 variants were identified in older patients (Table). [Formula presented] Conclusions: Early-onset CRC was characterized by a higher proportion of tumors without detectable genetic mutations, whereas later-onset CRC more often demonstrated mutations in BRAF, NRAS, and MLH1. These findings highlight that younger patients may develop CRC through alternative or as-yet-undefined molecular mechanisms, underscoring the need for further investigation into age-specific pathways of tumorigenesis and their implications for screening and treatment strategies.

Volume

106

Issue

3

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