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The Influence of Diet and Genetic Polymorphisms on Susceptibility to Colorectal Adenomas


This project investigates the influence of diet and genetic factors on susceptibility to colorectal adenomas and factors that predispose certain adenomas to become colorectal cancers.

<p>Colorectal cancer is a major cause of cancer mortality which has been linked to specific dietary and environmental factors.

<p>Individual susceptibility to colorectal cancer is thought to be determined, at least in part, by inheritance of specific variants of a range of polymorphic drug metabolising enzymes, responsible for the metabolic activation and detoxification of carcinogenic substances present in the diet and environment.

<p>Despite advances in the understanding of the molecular genetics of colorectal tumours, survival rates from colorectal cancer have not improved significantly in the last decade and it is important to attempt to seek ways of identifying at risk individuals at an early, often asymptomatic stage to increase survival.

<p>To this end, the UK Government commissioned a pilot faecal occult blood (FOB) screening programme to detect early adenomas.

<p>The Scottish arm of this project is being conducted in Tayside, Grampian and Fife where this screening programme is taking place.

<p>This work follows on from the previous FSA funded multi-centre collaborative study (T01003/4/5), which investigated whether individual differences in the ability to metabolise dietary heterocyclic amine carcinogens, present in red meat, contributes to colorectal cancer susceptibility.

<p>This current project builds on this previous study and the techniques it developed using two of the teams involved in the previous study.

<p>It aims to assess whether genetic polymorphisms contribute to individual susceptibility to pre-malignant adenoma formation.

More information

Individuals participating in the FOB trial are being invited to participate in this study and are providing both study samples and controls.

<p>Individuals who test positive in an FOB test but are then shown not to have polyps are being asked to serve as negative controls, those with polyps form the 'positive' individuals.

<p>Individuals are being asked to complete current dietary information (using a Food Frequency Questionnaire) and lifestyle information using similar questionnaires to those used in the previous study.

<p>Blood and biopsy samples will be assessed for individual pharmacogenetic profiles, and an assessment of mutation spectra and microsatellite instability in early adenomas will be examined in an attempt to identify individuals at risk for adenoma formation and also for progression to colorectal cancer.

<p>This may make it possible to identify genetic or dietary factors that determine whether a particular adenoma will progress to become a tumour or not.

<p>Such an understanding of the genetic and environmental factors which determine susceptibility to adenoma formation raises the possibility that high risk individuals may be identified at an early stage where appropriate dietary intervention may influence disease progression.

<p>Find more about this project and other FSA food safety-related projects at the <a href="; target="_blank">Food Standards Agency Research webpage</a>.

University of Dundee
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