Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4

• Published in: British journal of cancer Vol. 126; no. 2; pp. 297 - 301
• Main Authors: Ouahoud, Sarah, Jacobs, Rutger J., Kodach, Ludmilla L., Voorneveld, Philip W., Hawinkels, Lukas J. A. C., Weil, Nikki L., van Vliet, Britt, Herings, Ron M., van der Burg, Lennart R. A., van Wezel, Tom, Morreau, Hans, Slingerland, Marije, Bastiaannet, Esther, Putter, Hein, Hardwick, James C. H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2022; Nature Publishing Group
• Subjects: 692/4028/67/2195; 692/699/1503/1504/1885; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Colorectal Neoplasms - prevention & control; Drug Resistance; Epidemiology; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Incidence; Male; Middle Aged; Molecular Medicine; Mutation; Netherlands; Oncology; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Smad4 protein; Smad4 Protein - genetics; Smad4 Protein - metabolism; Statins; Netherlands
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-021-01604-6

Background Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin use and the risk of developing colorectal cancer of a particular molecular subtype. Methods By linking two registries unique to the Netherlands, 69,272 statin users and 94,753 controls were identified and, if they developed colorectal cancer, their specimens traced. Colorectal cancers were molecularly subtyped according to the expression of SMAD4 and the mutation status of KRAS and BRAF . Results Statin use was associated with a reduction in the risk of developing colorectal cancer regardless of molecular subtype (HR 0.77; 95% CI 0.66–0.89) and a larger reduction in the risk of developing SMAD4-positive colorectal cancer (OR 0.64; 95% CI 0.42–0.82). There was no relationship between statin use and the risk of developing colorectal cancer with a mutation in KRAS and/or BRAF . Conclusions Statin use is associated with a reduced risk of developing colorectal cancer with intact SMAD4 expression.