RESUMO
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.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Smad4/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteína Smad4/genéticaRESUMO
Colorectal cancer (CRC) is primarily a lifestyle disease of the western world. As such it can be likened to cardiovascular disease and indeed it shares many of the same risk factors. It is therefore perhaps unsurprising that cholesterol metabolism and colorectal cancer are also intricately linked. Many of the initial studies suggesting a link between dietary cholesterol, blood cholesterol levels and cholesterol lowering drugs were performed more than a decade ago. The most recent insights in this field are the result of meta-analyses, advances in pharmacogenetics and the new field of molecular pathological epidemiology. This review summarises the current evidence linking cholesterol metabolism with colorectal cancer including the suggested underlying molecular causes and the implications for colorectal cancer prevention.