Chemo- and dietary prevention of colorectal cancer.

Because of the substantial morbidity and mortality associated with colorectal cancer, and the limitations and costs of treating this disease, prevention remains a desirable (if elusive) goal. In this paper, we discuss both chemo- and dietary prevention strategies for colorectal cancer, recognising the overlap and cross-fertilisation between these two approaches. Chemopreventive compounds are drugs and are developed for clinical use like other pharmaceuticals. A formal sequential multi-phase programme for development of chemopreventive agents has been instituted by the National Cancer Institute, U.S.A. This involves both preclinical efficacy and clinical studies. Such studies increasingly employ preneoplastic intermediate markers (such as proliferation measures) as well as neoplastic adenomas as endpoints. Promising chemopreventive agents include calcium, aspirin and other non-steroidal anti-inflammatory drugs, vitamins (such as vitamin E and folate), 2-dimethylfluorornithine (DFMO), oltipraz and ursodeoxycholic acid. Several lines of evidence implicate diet in colorectal carcinogenesis. Key hypotheses in diet and colorectal cancer (which are amenable to prevention, research and action), in addition to those pertaining to the micronutrient chemopreventives, include dietary fat and fibre, food mutagens, red meat, and overall low-fat, high-fibre, high fruit and vegetable dietary patterns and cuisines. Several adenomatous polyp recurrence studies with fibre supplement, macronutrient or dietary pattern interventions have been undertaken internationally. We review early findings from this new generation of studies, and anticipate the future results from these investigations and the ambitious Women's Health initiative in the U.S.A. Results from these studies may convert the promise of colorectal cancer prevention into reality.