On the mechanisms relevant to nutritional carcinogenesis.

Prevention of the nutritionally linked cancers will be on a sounder footing eventually if the measures recommended not only are consonant with international epidemiological data and the results of laboratory experimentation, but also rest on an understanding of the mechanisms of action of the various nutritional factors. The process of cancer causation involves a series of steps that can be classified broadly into (a) the definition of DNA-reactive carcinogens and (b) the assessment of enhancing or inhibiting epigenetic agents. For cancers highly prevalent in the Western world, especially of the breast, colon, and pancreas, and perhaps also of the prostate, evidence has begun to accrue that a new type of heterocyclic amine formed during cooking of meat or fish constitutes the DNA-reactive carcinogen. The type and amount of fat play a role in enhancing the effect of epigenetic mechanisms that characteristically are highly sensitive to dosage and duration. These epigenetic phenomena are also reversible. Cereal fiber, by increasing stool bulk, dilutes epigenetic promoters in the intestinal tract. Therefore, based on mechanistic understanding, reduction in risk is feasible by lowering fat, increasing fiber, and perhaps by altering cooking modes.