The Fourth DeWitt S. Goodman lecture. Novel approaches to the prevention of colon cancer by nutritional manipulation and chemoprevention.

Large bowel cancer is one of the most common human malignancies in Western countries including North America. This report details the preventive strategies aimed at reducing the incidence and mortality of large bowel cancer by nutritional manipulation and chemopreventive agents. During recent decades, multidisciplinary research in epidemiology and laboratory animal model studies have contributed much to our understanding of the etiology of this cancer; more importantly, it has enabled us to approach cancer prevention. An impressive body of data thus far accumulated has provided important concepts about dietary factors such as fat and fiber as key modulators of large bowel cancer. Compelling experimental evidence indicates that certain dietary lipids and fibers influence tumorigenesis in the colon. Data obtained in metabolic epidemiological and laboratory animal model studies are sufficiently convincing in showing the enhancement of colon cancer by certain types of fat and protection against it by certain dietary fibers. Our approach to the primary prevention of large bowel cancer is to translate the findings from clinical epidemiological and laboratory studies into sound advice for patients and for the public at large to reduce fat intake and increase fiber intake, specifically cereals and grains. Preclinical efficacy studies have provided scientifically sound evidence as to how several phytochemicals and their synthetic analogues act to retard, block, or reverse carcinogenesis. Equally exciting are opportunities for effective chemoprevention with nonsteroidal anti-inflammatory agents, both synthetic and naturally occurring, or selective cyclooxygenase-2 inhibitors. Our exploration of the multistep process of carcinogenesis has provided substantial insights into the mechanisms by which chemopreventive agents modulate these events. Growing knowledge in this area has brought about an innovative combination of agents with different modes of action as a means of increasing efficacy and minimizing toxicity. There is growing optimism for the view that realization of preventive concepts in large bowel cancer will also serve as a model for preventing malignancies such as cancer of the prostate and breast.