The CAPP studies

Colorectal cancer is second only to lung cancer as a cause of cancer death. Up to 20% of cases are attributed to genetic predisposition, with 5% due to mutations in the APC gene or the mismatch repair genes causing familial adenomatous polyposis (FAP) and Lynch Syndrome (HNPCC) respectively. Colon cancer is one of the most common inherited cancer syndromes known. The genes known to be involved in colorectal cancer are MSH2 and MSH6 both on chromosome 2 and MLH1 on chromosome 3. Normally the protein products of these genes help to repair mistakes made in DNA replication. If the MSH2, MSH6 and MLH1 proteins are mutated and therefore don't work properly, the replication mistakes are not repaired, leading to damaged DNA, and in this case colon cancer. Dietary factors have been observed to be a major reason why so many people develop this disease in developed countries. It has been observed that regular users of non-steroidal anti-inflammatory drugs (such as aspirin) are at a significantly reduced risk. The CAPP studies aim to try and prove if these observations are true.

CAPP1-FAP

CAPP1 commenced in 1993 in 34 European countries and closed recruitment in 2002. Carriers of familial adenomatous polyposis (FAP) were recruited to a randomised controlled trial of 600mg aspirin and/or 30g resistant starch. In total 206 FAP carriers received treatment. Completed data on 133 subjects, followed for 1 year, have now been analysed. Neither intervention resulted in a significant reduction in polyp number as assessed either by the endoscopist or blinded review of rectal videos. The mean size of largest polyps was, however, significantly reduced in the aspirin only group (p=0.01). A secondary analysis using data from those who had stayed more than one year, suggesting higher compliance. Here, both aspirin alone and the combined aspirin/resistant starch group achieved significance (p=0.04 and p=0.03). Those treated with starch had significantly shorter crypts (p<0.0001,95% CI 0.87,0.96); those treated with aspirin had longer crypts and a 37% increase in crypt cell proliferation. These data suggest that aspirin and resistant starch are protective against cancer but with different modes of action. Aspirin may act later, preventing progression of small adenomata. FAP carriers are an ideal study group since their molecular defect is shared with a majority of sporadic colorectal cancers and any FAP chemoprevention strategy is likely to have general relevance. Such studies need sustained infrastructure investment as planned by the new International Society for Gastrointestinal Hereditary Tumours - InSiGHT.

For detailed information please visit the website at: http://www.capp2.com

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