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The association of dietary fat intake with acquired genetic abnormalities in the colorectal mucosa - AN0216

Epidemiological evidence suggests that the type and quantity of dietary fat is a major risk factor for colorectal cancer. In order to improve our understanding of this relationship and to achieve accurate and well focussed dietary advice, it is essential to determine the link between fatty acid intake and the acquired genetic damage which eventually leads to neoplasia. The purpose of this project is to test the hypothesis that the pattern of dietary fat intake influences the type and frequency of oncogene mutations associated with common precancerous lesions of the human colorectum. The project comprises two stages: 1) An investigation of the relationship between habitual fat intake and the frequency of k-ras and p53 mutaitons in adenomatous polyps or tumours recovered at andoscopu or surgery. 2) A study of the impact of supplementation with polysunsaturated fatty acids of the n-3 series on the site of mitosis in normal crypts and the recurrence of mucosal lesions.
1. To test the hypothesis that dietary fat consumption increases the risk of colorectal cancer by promoting particular mutations in the mucosal cells, and that particular combinations of such mutations are more likely in patients consuming high levels of saturated fat. 2) To test the hypothesis that abnormalities in the spatial distribution of mitosis in otherwise normal crypts in the human colonic mucosa are associated with the emergence of particular mutations in adjacent focal lesions and that PHFA of the n-3 series can normalise this abnormality and reduce the recurrence of such lesions. 3. TO develop improved dietary guidelines for the avoidance of colorectal cancer and / or develop new hypotheses for further research. 4. To develop protocols and extablish a data and tissue base for future studies on the relationship between diet and the genetic corellates of colorectal cancer.
Time-Scale and Cost
From: 1994

To: 1998

Cost: £445,551
Contractor / Funded Organisations
IFR - Institute of Food Research (BBSRC)