Environmental carcinogens and large bowel cancer

Abstract

THE geographical variation in the incidence of large bowel cancer together with the increased incidence found in migrants from low risk to high risk areas support the view that environmental factors are involved in the aetiology of this disease¹. These environmental factors are thought to be largely dietary although other influences have not been excluded. Aries et al.² suggested that the disease is caused by carcinogens produced by gut bacteria from bile acids. Diet would influence both the bile acid levels in the bowel and also the nature of the gut flora. Faecal bile acids are more concentrated in faeces from people living in high incidence areas than in faeces from populations at low risk³. Similarly, faecal bile acids are usually more concentrated in samples from patients with large bowel cancer than in those from control patients⁴. Bile acids were postulated to be the substrates from which the gut flora produced carcinogens² and indeed this suggestion has been supported by the demonstration that the faecal concentration of bacterially degraded bile salts is more highly correlated with the incidence of large bowel cancer than is the total bile acid level³. However, it has been suggested that the primary role of bile acids is as co-carcinogens and this suggestion is supported by the results of animal experimentation demonstrating the promoting effect of bile acids on the action of known carcinogens⁵. If it is accepted that bile acids act as co-carcinogens it becomes necessary to explain how the carcinogen reaches the large bowel without producing cancers in other parts of the gastrointestinal tract. Here we describe preliminary investigations of a mechanism by which an environmental carcinogen could be transported to the large intestine.