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Volume 26
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10.3390/ijms26167893
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort

by
Lisa Padroni
1,
Giorgia Marmiroli
2,
Laura De Marco
3,
Valentina Fiano
2,
Lucia Dansero
1,
Saverio Caini
4,
Giovanna Masala
5,
Luca Manfredi
1,
Lorenzo Milani
1,
Fulvio Ricceri
1 and
Carlotta Sacerdote
6,7,*
1
Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, 10043 Turin, Italy
2
Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
3
Unit of Cancer Epidemiology, Città Della Salute e Della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
4
Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy
5
Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy
6
Department of Health Sciences, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy
7
Unit of Epidemiology, Local Health Unit of Novara, Viale Roma, 7, 28100 Novara, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(16), 7893; https://doi.org/10.3390/ijms26167893
Submission received: 9 July 2025 / Revised: 12 August 2025 / Accepted: 13 August 2025 / Published: 15 August 2025
(This article belongs to the Section Molecular Biology)
Review Reports Versions Notes

Abstract

Circulating microRNAs (miRNAs) have emerged as non-invasive biomarkers that may be associated with cancer risk, but their role in the development of colon cancer is still not well understood. We conducted a nested case-control study within the EPIC-Italy cohort to investigate the association between pre-diagnostic serum levels of eight candidate miRNAs (Let7, Mir21, Mir155, Mir181, Mir222, Mir145, Mir92, and Mir20) and subsequent colon cancer occurrence. A total of 104 incident colon cancer cases were matched to 104 controls by center, sex, age, recruitment date, and vital status. miRNA expression was quantified using RT-qPCR and normalized to Mir484. Logistic regression models were applied to estimate odds ratios, 95% confidence intervals, and p-values, adjusting for age at recruitment, smoking status, body mass index, physical activity, adherence to a Mediterranean diet, and socioeconomic position. Elevated expression of Let7 (OR = 0.91; 95% CI: 0.84–1.00; p = 0.04) was associated with slightly lower odds of colon cancer in unadjusted models. Mir21 and Mir222 showed borderline associations (p = 0.07 and p = 0.09, respectively), but these did not remain significant after Bonferroni correction. This result was consistent in the multivariate logistic model: higher levels of Let7 (OR = 0.91; 95% CI: 0.82–1.00; p = 0.06) and Mir222 (OR = 0.75; 95% CI: 0.57–1.00; p = 0.05) are suggestive of an association with lower odds of colon cancer. Our findings highlight the challenges of using circulating miRNAs as very early biomarkers, particularly when samples are collected nearly a decade before diagnosis. Future studies with larger sample sizes, serial blood collections, and integration with inflammatory and immune markers will be crucial to clarify the temporal dynamics of circulating miRNA alterations and their potential role in risk-adapted screening strategies.
Keywords: colon cancer; microRNA; nested case-control study colon cancer; microRNA; nested case-control study

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MDPI and ACS Style

Padroni, L.; Marmiroli, G.; De Marco, L.; Fiano, V.; Dansero, L.; Caini, S.; Masala, G.; Manfredi, L.; Milani, L.; Ricceri, F.; et al. Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort. Int. J. Mol. Sci. 2025, 26, 7893. https://doi.org/10.3390/ijms26167893

AMA Style

Padroni L, Marmiroli G, De Marco L, Fiano V, Dansero L, Caini S, Masala G, Manfredi L, Milani L, Ricceri F, et al. Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort. International Journal of Molecular Sciences. 2025; 26(16):7893. https://doi.org/10.3390/ijms26167893

Chicago/Turabian Style

Padroni, Lisa, Giorgia Marmiroli, Laura De Marco, Valentina Fiano, Lucia Dansero, Saverio Caini, Giovanna Masala, Luca Manfredi, Lorenzo Milani, Fulvio Ricceri, and et al. 2025. "Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort" International Journal of Molecular Sciences 26, no. 16: 7893. https://doi.org/10.3390/ijms26167893

APA Style

Padroni, L., Marmiroli, G., De Marco, L., Fiano, V., Dansero, L., Caini, S., Masala, G., Manfredi, L., Milani, L., Ricceri, F., & Sacerdote, C. (2025). Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort. International Journal of Molecular Sciences, 26(16), 7893. https://doi.org/10.3390/ijms26167893

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