With respect to carcinogenesis, three aspects of the diet are of concern: (1) the content of exogenous carcinogens, (2) the endogenous synthesis of carcinogens from dietary components, and (3) the lack of protective factors.
• An example of an exogenous carcinogen is aflatoxin, which is an important factor in the development of hepatocellular carcinomas in parts of Asia and Africa. Exposure to aflatoxin causes a specific mutation (codon 249) in the TP53 gene in tumor cells. The mutation can be used as a molecular signature for aflatoxin exposure in epidemiologic studies.
The concern about endogenous synthesis of carcinogens or promoters from components of the diet relates principally to gastric carcinomas. Nitrosamines and nitrosamides are suspected to generate these tumors in humans, as they induce gastric cancer in animals. These compounds are formed in the body from nitrites and amines or amides derived from digested proteins. Sources of nitrites include sodium nitrite, added to foods as a preservative, and nitrates, present in common vegetables, which are reduced in the gut by bacterial flora. There is, then, the potential for endogenous production of carcinogenic agents from dietary components, which might well have an effect on the stomach.
High animal fat intake combined with low fiber intake has been implicated in the causation of colon cancer. The most convincing explanation for this association is as follows: High fat intake increases the level of bile acids in the gut, which in turn modifies intestinal flora, favoring the growth of microaerophilic bacteria. The bile acids or bile acid metabolites produced by these bacteria might serve as carcinogens or promoters. The protective effect of a high-fiber diet might relate to (1) increased stool bulk and decreased transit time, which decreases the exposure of mucosa to putative offenders, and (2) the capacity of certain fibers to bind carcinogens and thereby protect the mucosa. Attempts to document these theories in clinical and experimental studies have, on the whole, led to contradictory results.
• Vitamins C and E, β-carotenes, and selenium have been assumed to have anti-carcinogenic effects because of their anti-oxidant properties. To date, however, no convincing evidence has emerged to show that these antioxidants act as chemopreventive agents. As already mentioned, retinoic acid promotes epithelial differentiation and is believed to reverse squamous metaplasia.
Thus, despite many tantalizing trends and proclamations by “diet gurus,” to date there is no definite proof that diet in general can cause or protect against cancer. Nonetheless, concern persists that carcinogens lurk in things as pleasurable as a juicy steak and rich ice cream.
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Graham C, Mullen A, Whelan K: Obesity and gastrointestinal microbiota: a review of associations and mechanisms, Nutr Rev 73:376, 2016. [A review of the emerging data on the role of the microbiome in obesity.]