Role of bile acids and neutral sterols in familial cancer syndromes of the colon

Cholesterol is quantitatively the most significant sterol in mammalian tissues. The major metabolic pathway of this sterol leads to the formation of bile acids. The structural similarities between carcinogenic aromatic hydrocarbons and bile acids aroused the suspicion that bile acids might play a role in carcinogenesis. In familial polyposis, a condition with a strong genetic predisposition to colonic cancer, a failure to degrade fecal cholesterol and bile acids to secondary products has been postulated as a marker of the phenotypic expression of this condition. In contrast, epidemiologic studies in populations at high risk for colonic cancer, and consuming diets rich in animal fat, protein, and refined carbohydrates, show a positive correlation with high fecal concentrations of bile acids and their metabolites. The suggestion that secondary bile acids might act in concert with colonic carcinogens in promoting neoplastic transformation is supported by observations from experimental studies. Among the secondary bile acids, lithocholic acid is unique in that it has been shown to be comutagenic, promote cell transformation, and induce DNA strand breakage,in vitro. It has also been shown to bind covalently to tissue proteins in human liver and in livers of carcinogen-treated rats.