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Metabolic Syndrome Fuels Genomic Instability? Insights from a Pilot Study on Colorectal Cancer.
Salvatore Pezzino1,2, Maria Cristina Scuderi2, Ornella Coco2
1Department of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy.
Cancers
|November 27, 2025
Summary
Metabolic syndrome (MS) is linked to higher microsatellite instability (MSI) in colorectal cancer patients. This suggests metabolic health may influence cancer genetics, impacting immunotherapy selection.
Area of Science:
- Oncology
- Metabolic Disorders
- Genetics
Background:
- Metabolic syndrome (MS) affects 25% of adults globally.
- MS increases colorectal cancer (CRC) risk by 40%.
- Microsatellite instability (MSI) is a key biomarker for CRC immunotherapy selection.
Purpose of the Study:
- To investigate the correlation between metabolic syndrome (MS) and microsatellite instability (MSI) in colorectal cancer (CRC) patients.
- To explore potential shared pathways between metabolic dysfunction and genomic instability in CRC.
Main Methods:
- Pilot study of 157 surgically treated CRC patients.
- Classification of patients based on International Diabetes Federation MS criteria.
- Assessment of MSI via immunohistochemistry of mismatch repair proteins.
- Statistical analysis using chi-square tests and odds ratios.
Main Results:
- MS patients showed significantly higher MSI prevalence (15.5% vs. 9.8%, p < 0.05).
- MS was associated with a 1.63-fold increased odds of MSI.
- MSI co-occurrence with hepatic steatosis showed a strong association (OR: 5.81) within the MS group.
Conclusions:
- Initial evidence links MS to increased MSI frequency in CRC.
- Hepatic steatosis highlights potential common metabolic-genomic pathways.
- Metabolic assessment may aid immunotherapy selection in precision oncology, requiring further validation.
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