Nutrition and carcinoma of the large intestine.

Based on various lines of evidence and multi-disciplinary approaches, it has been suggested that nutrition and specific nutritional components, as well as dietary habits, in various parts of the world may play an important role in the causation and development of a number of major types of cancer. Nutrition may relate directly to the occurrence of 30-40% of cancers in men and 5 4 0 % of cancers in women in the USA and other Western countries (Hiatt et al. 1977; Doll & Peto, 1981; Magnus, 1982; Wynder et al. 1983). We have dissected the overall carcinogenic process into a number of sequential steps, all of which are necessary for a clinically invasive cancer to occur (Fig. I ) (Weisburger & Horn, 1981; Weisburger & Williams, 1981). This sequence has been demonstrated in numerous studies in animal models, and there is no reason to assume that this sequence would not also hold for the initiation, development, and progression of human cancers. In this scheme, the early events are the result of specific molecular changes caused by genotoxic carcinogens in cellular systems for cancers of the colon, breast, prostate, and perhaps even pancreas. We have noted that mutagens and also carcinogens are seen at the surface of fried or broiled foods such as meat or fish (Barnes et al. 1983; Sugimura et al. 1983). This concept, however, needs further validation through research currently being performed in a number of laboratories in Japan, Europe, and the USA. Gastric cancer, on the other hand, appears to be associated with totally distinct factors, namely, pickled and salted fish or beans and also residence in areas with geochemical or agricultural sources of nitrate intake, not balanced by the presence of vitamin C, vitamin E, or certain phenolic antioxidants and nitrite traps such as pyrogallol or tannins (Correa et al. 1982; Weisburger & Horn, 1982; Joossens & Geboers, 1983). The possible genotoxic carcinogen may be a nitrosamide or aryldiazonium salt. The formation of such compounds is inhibited by vitamin C, vitamin E and certain antioxidants (Mirvish, 1983). This fact can be used to decrease the risk of gastric cancer deliberately. Epigenetic or promoting agents play a major role in the development of cancers of the colon, breast and prostate (Reddy et al. 1980; Hill, 1983; Wynder et a1. I 983). Delineating the relevant epigenetic-promoting effects for cancer of the colon is important because whether or not overt invasive disease is seen depends a great deal on these epigenetic-promoting factors. These stem from the intake of appreciable amounts of dietary fat which are responsible for the endogenous production of specific non-genotoxic, epigenetic agents associated with increased risk.