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Validation of novel diet-related biomarkers of early colorectal neoplasia – use of proteomic technology and identification of mitochondrial DNA mutations [The BORICC Study]
Project Code: N12015
University of Newcastle
268 subjects were recruited, of which 55% were female. Subjects tended to be overweight or obese (mean BMI was 28.2 for men and 28.4 for women).
Using data on habitual food intake from a validated Food Frequency Questionnaire (FFQ), dietary patterns were established using Principle Components Analysis. A healthier eating pattern was identified that was characterised by higher consumption of Brassicas, cooked potatoes, fresh fruit, legumes and pulses, oily fish, vegetables and wholegrain foods, and lower intakes of beer, biscuits, confectionary, fried potatoes, processed meats, savoury snacks and white bread. A less healthy pattern was also established and was characterised by higher intakes of battered products, confectionary, fried potatoes, red and processed meats, and soft drinks and lower intakes of fresh and tinned fruit, wholegrain foods, and yoghurt. The unhealthy, but not the healthy, pattern significantly correlated with nutritional status measures.
Relationships between putative biomarkers of colorectal cancer (CRC) risk and the volunteer characteristics were investigated in regression models. Age, red cell folate and total energy intake were all positive predictors for mitochondrial Cox deficiency. Physical activity and a third dietary pattern were positive predictors of mitochondrial DNA mutation frequency. Plasma selenium was a negative predictor for mitotic activity in colo-rectal crypts, but telomere length had no significant dietary predictors. Some dietary factors, e.g. vitamin D status, were found to be predictors of the distribution of mitotic cells along the colo-rectal crypt; also, the unhealthy diet pattern was associated with an increased probability of apoptotic events.
2D-gel electrophoresis of extracts from 200 colorectal mucosal biopsies, identified 1678 individual protein spots. FFQ data showed a lack of significant associations with total meat, total fruits and vegetables, total non-starch polysaccharides intakes. Plasma CRP concentration (used as a marker of systemic inflammation) was strongly associated with mucosal proteins, the majority of which were acute-phase proteins. Colonic mucosal protein expression was also associated with plasma concentrations of arachidonic acid and total n-3 PUFA. Many of the proteins associated with plasma fatty acid concentrations were cytokeratins.
This project has generated a very large amount of data and has produced a substantial biobank (blood, buccal cells, mucosal biopsies and urine), which will be of value for future studies.
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