Sarah Ouahoud1, Rutger J Jacobs1, Ludmilla L Kodach1, Philip W Voorneveld1, Lukas J A C Hawinkels1, Nikki L Weil1, Britt van Vliet1, Ron M Herings2,3, Lennart R A van der Burg1, Tom van Wezel4, Hans Morreau4, Marije Slingerland5, Esther Bastiaannet5,6, Hein Putter7, James C H Hardwick8. 1. Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Utrecht, The Netherlands. 2. PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands. 3. Department of Epidemiology & Data Science, Utrecht, The Netherlands. 4. Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. 5. Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands. 6. Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands. 7. Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands. 8. Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Utrecht, The Netherlands. j.c.h.hardwick@lumc.nl.
Abstract
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.
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.
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