Journal Article

DKFZ-2025-02042

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Investigating the relationship of plasma microRNAs and colorectal cancer risk using genetic evidence.

Bouras, E. ; Papagiannopoulos, C. K. ; Mustafa, R. ; Sobieski, D. ; Schmit, S. L. ; Wu, A. H. ; Brenner, H.DKFZ* ; Li, C. I. ; Chan, A. T. ; Pellatt, A. J. ; Zheng, W. ; Keku, T. O. ; Moreno, V. ; Um, C. Y. ; Van Guelpen, B. ; Phipps, A. I. ; Pai, R. K. ; Lewis, S. J. ; Martin, R. M. ; Gunter, M. J. ; Peters, U. ; Dehghan, A. ; Tsilidis, K. K.

2025
BioMed Central London

Abstract: MicroRNAs (miRNAs) are short, single-stranded RNAs that function as post-transcriptional regulators of gene expression. Although circulating miRNAs have been linked to carcinogenesis, they have not yet been systematically investigated in relation to risk of colorectal cancer (CRC).We used Mendelian randomization (MR) and colocalization analyses to investigate the association of genetically predicted plasma miRNA concentrations (2083 miRNAs in 710 individuals) with risk of CRC (58,221 cases and 67,694 controls). For miRNAs associated with CRC risk, we also investigated their association with circulating plasma proteins (4907 proteins in 35,559 participants), bidirectionally, using MR. We performed pathway enrichment analysis (PEA) to explore downstream molecular pathways.Associations of five miRNAs with CRC were found in MR and supported in colocalization analyses. Specifically, miR-146a-5p, miR-21-5p, and miR-4707-3p were positively, and miR-1908-5p and miR-6810-3p were inversely associated with CRC risk. Several protein associations were found for these miRNAs (range of proteins with P < 0.05: 78-796; 211 with FDR < 5%), and 11 pathways were identified in PEA, including regulation of Erb-B2 receptor tyrosine kinase 4 (miR-6810-3p) and insulin-like growth factor pathways (miR-1908-5p).Our results support a potential implication of miR-146a-5p, miR-21-5p, miR-4707-3p, miR-1908-5p, and miR-6810-3p to CRC risk. However, their downstream effects should be elucidated before they can be utilized as preventive targets.

Keyword(s): Humans (MeSH) ; Colorectal Neoplasms: genetics (MeSH) ; Colorectal Neoplasms: blood (MeSH) ; MicroRNAs: blood (MeSH) ; MicroRNAs: genetics (MeSH) ; Mendelian Randomization Analysis (MeSH) ; Male (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Risk Factors (MeSH) ; Female (MeSH) ; Case-Control Studies (MeSH) ; Middle Aged (MeSH) ; Colorectal cancer ; Mechanisms ; Mendelian randomization ; MiRNA ; MicroRNA ; Proteins ; MicroRNAs

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Contributing Institute(s):

1. C070 Klinische Epidemiologie der Krebsfrüherkennung (C070)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2025

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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