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- Title
Aspirin reduces the incidence of metastasis in a pre-clinical study of Braf mutant serrated colorectal neoplasia.
- Authors
Kane, Alexandra M.; Liu, Cheng; Fennell, Lochlan J.; McKeone, Diane M.; Bond, Catherine E.; Pollock, Pamela M.; Young, Graeme; Leggett, Barbara A.; Whitehall, Vicki L. J.
- Abstract
<bold>Background: </bold>Aspirin reduces the incidence of conventional adenomas driven by APC mutation and thus colorectal cancer. The effect of aspirin on the ~20% of colorectal cancers arising via BRAF mutation is yet to be established.<bold>Methods: </bold>BrafV637E/+;Villin-CreERT2/+ mice were allocated to a control (n = 86) or aspirin-supplemented (n = 83) diet. After 14 months the incidence of murine serrated lesions, carcinoma and distant metastases were measured by histological examination. RNA was extracted from carcinomas from each cohort and subjected to sequencing to identify differentially expressed genes and molecular pathways.<bold>Results: </bold>Aspirin did not reduce the incidence of murine serrated lesions or carcinoma when compared to control, however, did significantly reduce lesion size (P = 0.0042). Among the mice with carcinoma there was a significant reduction in the incidence of distant metastasis with aspirin treatment (RR 0.69, 95% CI 0.48-0.90, P = 0.0134). Key pathways underlying metastasis of carcinoma cells include NOTCH, FGFR and PI3K signalling, were significantly downregulated in carcinomas sampled from mice on an aspirin-supplemented diet.<bold>Conclusions: </bold>Aspirin reduces the incidence of metastatic Braf mutant carcinoma, although this is not due to a reduction in primary disease. The reduction in metastasis could be attributed to a delay or prevention of molecular changes within the primary site driving metastatic growth.
- Subjects
BIOLOGICAL models; RESEARCH; GENETIC mutation; ANIMAL experimentation; RESEARCH methodology; ADENOMA; METASTASIS; DISEASE incidence; MEDICAL cooperation; EVALUATION research; COLORECTAL cancer; COMPARATIVE studies; ASPIRIN; TRANSFERASES; MICE; DEGENERATION (Pathology)
- Publication
British Journal of Cancer, 2021, Vol 124, Issue 11, p1820
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-021-01339-4