Dietary influences upon colon carcinogenesis.

A succession of case-control studies of diet and colon cancer, predominantly in developed countries, has produced varied and generally inconsistent findings. The somatic mutation theory of carcinogenesis has dominated much of cancer research for the past 30 years, encouraging emphasis on exogenous genotoxic agents capable of inducing malignant transformation via heritable damage to DNA. Increased risks of human cancers due to various potent chemical carcinogens (found in certain occupations), ionizing radiation, and sunlight have corroborated this "toxicological" view of cancer. Recently, however, greater emphasis has been paid to cancer as a disorder of growth control. The stimulation or derepression of cell growth, via hormones or proto-oncogene activation respectively, is likely to reflect "metabolic" disturbances--such as can be caused by diet. If diet influences large bowel carcinogenesis via mediating metabolic or biochemical factors such as intracolonic pH, production of bile acid metabolites, and fermentative production of volatile fatty acids (which appear to influence mucosal cell stability), then a variety of configurations of diet may have an equivalent net effect upon bowel carcinogenesis. Further, non-specific aspects of diet (such as total energy intake and frequency of eating) may be important; indeed, those two factors were found to be positively and independently associated with large bowel cancer (LBC) risk in our Adelaide case-control study. The accumulating evidence that other factors that alter sex hormonal status and/or hepatobiliary metabolism, and physical aspects of bowel function, are also associated with altered risk of LBC adds further credence to this metabolic model. Such factors are: gender, reproductive history and oral contraceptive usage in women, cholecystectomy, and physical activity.