Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk studyReportar como inadecuado




Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 10:99

First Online: 16 March 2010Received: 09 October 2009Accepted: 16 March 2010DOI: 10.1186-1471-2407-10-99

Cite this article as: Naguib, A., Mitrou, P.N., Gay, L.J. et al. BMC Cancer 2010 10: 99. doi:10.1186-1471-2407-10-99

Abstract

BackgroundBRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers.

Methods186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations. Diet and lifestyle data were collected prospectively using seven day food diaries.

ResultsBRAF V600E mutation was found in 15.6% of colorectal cancers but at higher frequencies in cancers with proximal location, poor differentiation and microsatellite instability MSI all p < 0.001. K-ras mutation mostly in codons 12 and 13 was found in 22.0% of colorectal cancers but at higher frequencies in cancers of more advanced Dukes- stage p = 0.001, microsatellite stable MSS status p = 0.002 and in individuals with lower blood high-density lipoprotein concentrations p = 0.04. Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent, however, K-ras mutation was found at higher frequencies in individuals with higher white meat consumption p < 0.001. Further analysis of specific mutation type demonstrated that G to A transitions in K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit p = 0.02.

ConclusionThese data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-99 contains supplementary material, which is available to authorized users.

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Autor: Adam Naguib - Panagiota N Mitrou - Laura J Gay - James C Cooke - Robert N Luben - Richard Y Ball - Alison McTaggart -

Fuente: https://link.springer.com/







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