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Age-Related Multigene Analysis of Colorectal Cancer Using Next-Generation Sequencing
Monika Kozlowska-Geller1, Łukasz Nawacki1, Monika Wawszczak-Kasza2,3
1Collegium Medicum, Jan Kochanowski University in Kielce, 25-317 Kielce, Poland.
Next-generation sequencing reveals distinct genetic profiles in colorectal cancer (CRC) based on patient age. Younger patients show more NRAS variants, while older patients have more KRAS alterations, impacting risk stratification and personalized therapy.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a significant global health concern with increasing incidence in younger populations.
- Next-generation sequencing (NGS) aids in identifying cancer-predisposing variants and molecular tumor alterations.
- Limited data exists on age-related genetic differences in CRC within Central and Eastern European populations, including Poland.
Purpose of the Study:
- To investigate molecular differences in colorectal cancer (CRC) between patients aged ≤50 and >50 years in a Polish cohort.
- To identify age-specific genetic alterations in tumor DNA using targeted sequencing.
- To explore the correlation between specific gene variants and patient prognosis.
Main Methods:
- Tumor DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue samples of 54 treatment-naive colorectal cancer patients.
- Targeted sequencing of 50 cancer-associated gene hotspots was performed using the AmpliSeq for Illumina Cancer Hotspot Panel v2.
- Variant frequencies were compared between younger (≤50 years) and older (>50 years) patient groups.
Main Results:
- Significant differences in variant frequencies were observed between age groups: KRAS mutations were more common in older patients (72.7% vs. 28.1%), while NRAS mutations were exclusive to younger patients (29% vs. 0%).
- TP53 variants were more frequent in younger patients (71.4% vs. 57.6%).
- 46% of patients displayed multiple gene alterations (≥3 mutations). IDH1 and CTNNB1 variants were associated with better prognosis, whereas TP53 variants indicated worse outcomes.
Conclusions:
- Multigene panel sequencing identified distinct age-related molecular patterns in colorectal cancer.
- Age-specific genetic alterations, such as NRAS in younger and KRAS in older patients, are significant.
- NGS-based multigene profiling is crucial for risk stratification and developing personalized therapies for CRC.
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