A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer

The primary endpoint will be the number, size and histological stage of colorectal carcinomas found after a minimum of 2 years treatment.

1. Adenoma size and number:
Elective removal of polyps will make fully developed cancers rare. The main outcome measure will be the number, size, location, villosity and dysplasia of adenomatous polyps
2. Apoptosis in adenomata:
A recent observation in the histology of an adenoma from a participant in CAPP1 has led us to consider that the pattern of apoptosis within adenomata is worthy of study. This is in keeping with the evidence in vivo and in vitro for an effect of aspirin on apoptosis. We will therefore request histopathological assessment of adenomas snared at colonoscopy, with special interest in signet cells and undifferentiated medullary carcinoma.
3. Cell proliferation and apoptosis in flat mucosa:
In a sub-set of participants, biopsies of flat rectal mucosa will be collected before and after treatment to test the hypothesis that altered cell proliferation (see Mills et al. 2001) and/or apoptosis is a reliable biomarker of tumorigenesis.
4. Other cancers:
Gene carriers of Lynch syndrome are at increased risk of many extracolonic cancers, and these will be systematically reported in the study group. In particular, there is a 42% lifetime risk of endometrial cancers in female gene carriers (Dunlop et al., 1997; Watson et al., 1994). These data are important in monitoring any favourable or unfavourable change in all cancers within the different study groups. In particular, it will be important to ascertain if the interventions might reduce colonic tumours while at the same time increasing upper gastrointestinal (GI) or non GI tumours. In mouse studies parallel to CAPP1, we have found a significant increase in small bowel polyps in APC knockout mice fed excess resistant starch (Burn et al., 1996). Aspirin reversed the effect. Regular aspirin use is associated with a reduced incidence of gastric cancer, a malignancy reported with increased frequency in Lynch syndrome families.