COLORECTAL CARCINOGENESIS

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Abstract
It is generally accepted that genetic and environmental factors combine in the aetiology of bowel cancer. Epidemiological studies have shown that the environmental factors effects are shown more clearly in the left colon, and that they are related to living in western societies whose diets contain high levels of protein, fat and energy. There has been recent awareness that consumption of alcoholic beverages, particularly beer, may be causally related to cancers of the left colon and rectum. This review attempts to relate the general epidemiological data to more specific mechanisms of colorectal carcinogenesis. Dimethylhydrazine (DMH) and N-nitroso chemicals are potent colorectal carcinogens in animals. They have not been thought very relevant to humans because their existence in appropriate forms in the environment has been debatable and analytical methods for the specific detection of non-volatile nitrosamines and nitrosamides have not been available. Recently, however, relevant alkylating activity has been detected in foods incubated in quasi-gastric conditions, and several epidemiological studies have shown a protective effect for Vitamin C, which may inhibit the development of rectal cancer through beer consumption. As Vitamin C prevents nitrosation and as precursors of nitrosamides are present in prepared foods, further dietary studies with hypotheses based on N-nitroso carcinogenesis are required. Unfortunately, these studies will probably not show clear dose-response relationships. Many of the complex reasons for this are discussed; however, one of the most important could be related to an interplay between inherited and environmental factors. The inherited factors demonstrated by chromosomal analysis in cancer and polyposis syndromes are a reminder that other genetic (oncogenetic) changes may occur in sporadic colorectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

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