Colibactin-associated mutations in the human colon appear to reflect anatomy and early exposure, not oncogenesis
, were significantly enriched in the rectum of donors with and without polyps (adjusted p-values < 0.01). Moreover, when comparing findings to crypts from individuals with CRC and sequenced CRC tumors, we observed consistent enrichment of the colibactin-associated mutational signature "ID18" in the rectum in both normal colon crypts and CRC tumors, without significant difference in colibactin-specific single nucleotide variant or insertion-deletion burden in crypts across the three clinical groups (i.e., no polyp, polyp, and CRC). These findings argue against a causal or prognostic role for colibactin in CRC, instead indicating that the proposed association with early-onset disease reflects anatomic specificity rather than cancer-specific clinical relevance.
Authors
- Hannah C. Happ (ORCID: https://orcid.org/0000-0002-8266-266X)
- Amiko M. Uchida (ORCID: https://orcid.org/0000-0003-2171-4769)
- James M. Hotaling (ORCID: https://orcid.org/0000-0002-4401-4565)
- Deborah W. Neklason (ORCID: https://orcid.org/0000-0002-4546-7080)
- Alexis Garretson (ORCID: https://orcid.org/0000-0002-7260-0131)
- Joshua L. Mincer (ORCID: https://orcid.org/0000-0002-0351-6163)
- Laurel Hiatt (ORCID: https://orcid.org/0000-0003-1321-0325)
- Thomas A. Sasani (ORCID: https://orcid.org/0000-0003-2317-1374)
- Aaron R. Quinlan (ORCID: https://orcid.org/0000-0003-1756-0859)
- Akshay Kumar Avvaru (ORCID: https://orcid.org/0000-0003-4698-9363)
- Camila L. Goclowski (ORCID: https://orcid.org/0009-0002-1327-0424)
- Elizabeth V. Peterson
Institutions
- University of Utah (US)
- University of Colorado Anschutz Medical Campus (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-04-15
- DOI
- https://doi.org/10.64898/2026.04.13.26350783
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00