An international team led by researchers at the University of California San Diego sequenced 981 colorectal cancer genomes from 11 countries, searching for mutation patterns that might differ by geography or by a patient's age at diagnosis.
A mutation signature caused by colibactin, a DNA-damaging toxin made by certain gut bacteria, was more common in countries with higher colorectal cancer rates. It was also 3.3 times more common in patients diagnosed before age 40 than in those diagnosed after 70, and the colibactin mutations arose early in the tumors' development.
Colibactin exposure was further linked to mutations in a specific cancer-driving gene, APC, responsible for about a quarter of its driver insertions and deletions in colibactin-positive tumors. The study shows an association between a bacterial toxin's mutational fingerprint and early-onset cases, not direct proof that the bacteria alone cause the cancer, and what drives higher colibactin exposure in some countries or some children is still unknown.
Read the original study
Díaz-Gay et al., Nature, 2025 · doi.org/10.1038/s41586-025-09025-8
The damage was written early into the tumor.
Source
- Díaz-Gay, M., Dos Santos, W., Moody, S., Kazachkova, M., Abbasi, A., Steele, C. D., Vangara, R., Senkin, S., Wang, J., Fitzgerald, S., Bergstrom, E. N., Khandekar, A., Otlu, B., Abedi-Ardekani, B., de Carvalho, A. C., Cattiaux, T., Penha, R. C. C., Gaborieau, V., Chopard, P., . . . Alexandrov, L. B. (2025). Geographic and age variations in mutational processes in colorectal cancer. Nature, 643(8070), 230–240. https://doi.org/10.1038/s41586-025-09025-8