N12017: Protein acetylation as a diet-modifiable biomarker of colorectal cancer risk
Wednesday 21 June 2006
This research project aims to identify novel biomarkers of preclinical carcinogenesis and investigate the extent to which these biomarkers are responsive to dietary intervention.
Background
Enzymes governing protein acetylation are altered in many cancers and their activities are known to be influenced by the dietary fibre fermentation products butyrate and propionate.
There is strong epidemiological evidence that dietary 'fibre' (non-starch polysaccharide (NSP) and resistant starch (RS)) is protective against colorectal cancer. Protein acetylation is one mechanism whereby colorectal cancer risk is potentially modifiable by fibre. Colonic fermentation of RS and NSP yields short chain fatty acids (SCFAs) including butyrate, which is crucial to the maintenance of colonic health. Butyrate has been shown to inhibit histone deacetylases leading to changes in gene expression through altered protein function resulting from changes in protein acetylation.
Research Approach
The study is divided into two major tasks:
a) An observational study (n=90) of protein acetylation in the colon in healthy volunteers, adenoma and carcinoma patients, using a mass-spectrometry-based approach
b) An intervention study with normal (n=20) and polyp (n=20) patients with low fibre intakes who will be recruited to a 8 week high fibre intervention to analyse the effects of increasing SCFA on protein acetylation in the colon.
The project will therefore identify biomarkers of CRC (from a) including a subset which may be responsive to dietary intervention (from b).