a1 Human Nutrition Research Centre, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK
a2 Institute of Human Genetics, University of Newcastle, Bioscience Centre, Times Square, Scotswood Road, Newcastle upon Tyne, NE1 4EP, UK
a3 Genetic Epidemiology Division, Cancer Research UK, University of Leeds, Cancer Genetics Building, St James's University Hospital, Leeds LS9 7TF, UK
Loss of function of the adenomatous polyposis coli (APC) tumour suppressor gene through truncating mutations or other means is an early event in most colo-rectal cancer (CRC). The AFC gene encodes a large multifunctional protein that plays key roles in several cellular processes, including the wnt signalling pathway where an intact APC protein is essential for down regulation of β-catenin. The APC protein also plays a role in regulation of cell proliferation, differentiation, apoptosis, cell-cell adhesion, cell migration and chromosomal stability during mitosis. Acquisition of a non-functional APC gene can occur by inheritance (in the disease familial adenomatous polyposis (FAP)) or by a sporadic event in a somatic cell. Whilst there is strong epidemiological evidence that variation in diet is a major determinant of variation in CRC incidence, conventional adenoma recurrence trials in sporadic cases of the disease have been relatively unsuccessful in identifying potentially protective food components. Since the genetic basis of CRC in FAP and in sporadic CRC is similar, intervention trials in FAP gene carriers provide an attractive strategy for investigation of potential chemo-preventive agents, since smaller numbers of subjects and shorter time frames are needed. The Concerted Action Polyp Prevention (CAPP) 1 Study is using a 2×2 factorial design to test the efficacy of resistant starch (30 g raw potato starch-Hylon VII (1:1, w/w)/d) and aspirin (600 mg/d) in suppressing colo-rectal adenoma formation in young subjects with FAP. Biopsies of macroscopically-normal rectal mucosa are also being collected for assay of putative biomarkers of CRC risk.