Experimental approaches to colon cancer prevention in humans

Colorectal cancer is a major illness in the Western world. International and migrant studies suggest that environmental causes, notably a fat- and calorie-dense diet (even if adopted in adulthood), are associated with the disease. Case-control studies have not conclusively identified specific etiologic dietary factors, however. In addition, the emphasis placed on migrant studies has led many to overlook potentially important genetic factors that might help to explain some of the discrepancies in the epidemiologic data. Thus, the cause(s) of colorectal cancer remain unclear and hence effective preventive strategies are not presently available. Numerous tenable hypotheses have been generated as a consequence of observational and analytical epidemiologic studies, as well as rodent experiments. Controlled trials to test these hypotheses using colorectal cancer as an endpoint are not justifiable at present. It is possible, however, that "intermediate markers" (such as epithelial cell proliferation rates and others) that are associated with colorectal cancer in both humans and experimental animal systems might provide the means for hypothesis testing in short-term clinical trials. Despite the fact that this approach has several caveats, consistent results obtained in short-term studies would more readily justify the undertaking of a large-scale, long-term controlled study using colon cancer or adenomatous polyp recurrence as an endpoint.