Age-Related Multigene Analysis of Colorectal Cancer Using Next-Generation Sequencing

Background. Colorectal cancer (CRC) remains a major global public health problem, particularly in Western countries. The imple-mentation of next-generation sequencing (NGS) has enabled multigene panel analysis to identify cancer-predisposing variants and characterize molecular alterations in tumors. To investigate molecular differences in CRC between patients younger than 50 years and those older than 50 years. Methods. Inclusion criteria were the absence of prior radio- or chemotherapy and availability of DNA suitable for NGS. Patients were divided into two age groups: ≤50 years and >50 years. DNA was extracted from FFPE tissue samples. Targeted sequencing was performed using an Illumina hotspot cancer panel comprising 50 genes (700 amplicons). Results. Mutation frequencies in younger vs. older patients were: TP53 (76% vs. 64%), APC (57% vs. 45%), KRAS (43% vs. 73%), NRAS (29% vs. 0%), SMAD4 (9% vs. 15%), PIK3CA (14% vs. 33%), FBXW7 (5% vs. 15%). Co-occurrence of APC/KRAS/TP53 mutations was observed in 20% of cases. KRAS mutations were significantly more frequent in older patients (p=0.001), while NRAS mutations occurred exclusively in younger patients (29% vs. 0%, p=0.021). Overall, 46% of patients exhibited multiple gene alter-ations (≥3 mutations). Notably, IDH1 and CTBX1 mutations were found only in patients with better prognosis, whereas TP53 mu-tations were nearly twice as common in patients with worse outcomes. Conclusions. Multigene panel sequencing revealed distinct age-related molecular patterns in CRC. Younger patients were more likely to harbor NRAS mutations, whereas KRAS alterations predominated in older individuals. These findings underscore the relevance of NGS-based multigene profiling for risk stratification and personalized therapy in colorectal cancer.