Corfe, B.M., Williams, E.A., Bury, J.P., Riley, S.A., Croucher, L.J., Lai, D.Y.L. and Evans, C.A. (2009) A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study. BMC Cancer, 9. Art No.332. ISSN 1471-2407Full text available as:
Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention.
Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division.
Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function.
|Copyright, Publisher and Additional Information:||© 2009 Corfe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Keywords:||Genotoxin-induced apoptosis; Colorectal-cancer; Resistant starch; Sodium-butyrate; Up-regulation; Proliferation; Rat; Pig; Deacetylase; Recurrence|
|Institution:||The University of Sheffield|
|Academic Units:||The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Process Engineering (Sheffield)
The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield)
The University of Sheffield > Faculty of Social Sciences (Sheffield) > Department of Geography (Sheffield)
|Depositing User:||Miss Anthea Tucker|
|Date Deposited:||29 Oct 2009 15:01|
|Last Modified:||09 Jun 2014 00:16|