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Concerted Action Polyp Prevention 2. A randomised controlled trial of colorectal polyp and cancer prevention using aspirin in carriers of hereditary non-polyposis colon cancer: HNPCC

Objective

Objectives:
? CAPP2 will be the first randomized controlled trial to test the hypothesis that regular oral aspirin and/or resistant starch will inhibit colorectal adenoma development and growth in carriers of Hereditary Non-Polyposis Colon Cancer (HNPCC), a population at high risk of colon cancer.
? CAPP2 will disseminate advanced mutation detection techniques.
? CAPP2 will help to harmonize European HNPCC registries.

Brief Description:
Colon cancer is the commonest cause of cancer death after lung cancer. Environmental factors play a major role but in a significant minority genetic studies reveal an inherited predisposition. Recent studies have identified defects in mismatch repair genes in families with clinical features of hereditary non-polyposis colon cancer, which may account for up to 5% of colon cancer. Carriers of HNPCC are an ideal population in which to test preventive strategies; they are under regular follow-up, are motivated and are representative of the group most likely to follow future dietary or therapeutic recommendations.

Carriers will be identified on the basis either of being a member of a known HNPCC family and having developed a typical tumour or following demonstration of a pathological mismatch repair gene defect. The aspirin hypothesis arises from a body of evidence including large scale epidemiological studies, animal studies, in vitro analysis of aspirin in colon cancer cells, and small scale human intervention studies using other non-steroidal anti-inflammatory drugs (NSAIDs) such as sulindac. Resistant starch is carbohydrate which reaches the colon undigested, there to be fermented to short chain fatty acids such as butyrate. Popuiations with a high starch intake have reduced colon cancer risks and butyrate is anti-neoplastic in vitro. A continuing project initiated under BIOMED 1 is testing similar interventions in carriers of Familial Adenomatous Polyposis, an autosomal dominant disorder characterized by the appearance of hundreds of colonic polyps in the teens and almost inevitable progression to colon cancer in early adulthood. This project, known as CAPP1 (Concerted Action Polyp Prevention 1 ) was adopted by the UK Medical Research Council and has recruited, to date, 150 patients across Europe. The starch used in this project is analogous to the resistant starch used in CAPP1 but the form used is improved and can be taken with cooked food. Using a factorial design, the effects on polyp development and growth of 20 grams of resistant starch and/or 600 mg of enteric coated aspirin will be assessed. CAPP2 has the support of the International Collaborative Group on HNPCC with worldwide membership. Through the European and associated countries in this network it is intended to identify 1000 to 1200 gene carriers eligible for enrolment.

Keywords:
colon cancer, HNPCC, mismatch repair genes, aspirin, resistant starch, randomized controlled trial

Funding Scheme

CON - Coordination of research actions

Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Address
Claremont Place 19-20
NE2 4AA Newcastle - Upon Tyne
United Kingdom