The role of genotoxic carcinogens and of promoters in carcinogenesis and in human cancer causation.

Abstract

The majority of human cancers have multifactorial environmental causes stemming mainly from lifestyle factors such as use of tobacco products through cigarette smoking, snuff dipping, or chewing, and specific nutritional elements and dietary practices. The mechanisms of these lifestyle factors can be analyzed in terms of specific genotoxic carcinogens, and of epigenetic agents or promoting factors. Tobacco and tobacco smoke contain not only genotoxic carcinogens but also, with a more important ultimate effect, cocarcinogens and promoters. Alcohol acts as a cocarcinogen with tobacco, possibly by modifying the metabolism of carcinogens in select organs. Genotoxic carcinogens as nutritional factors may be found in pickled, salted, and smoked foods and may be responsible for gastric cancer. Vitamins C and E and other antioxidants are effective inhibitors. Other types of genotoxic carcinogens are mutagenic chemicals found in broiled and fried foods, and these may be involved in cancer of the colon, breast, and prostate. Promoting effects derive from a high level of dietary fat, which has been linked epidemiologically and through laboratory studies to a higher risk for these cancers. Possible mechanisms by which fat exerts its effects are an increased concentration of bile acids in the stool, as related to colon cancer, and which may be countered by a high cereal fiber diet, to increase stool bulk. In relation to breast or prostate cancer, fat may exert its effect on complex hormonal balances, and also on membrane composition. These promoting effects, whether associated with tobacco smoke or nutrition, are highly dose-dependent, and provided the insult is not too far advanced, reversible. Thus, lowering the dosage, or eliminating the effect as in smoking cessation should have an appreciable effect in reducing overt disease development, and do so fairly promptly. This may apply also to a reduction of second disease in cases where a first occurrence has been successfully treated by conventional means.