Etiology and Pathogenesis



The cause of colonic cancer is not known, but there are certain interesting associations. The geo­graphical differences in incidence noted above, together with shifts in incidence in migrant groups, strongly suggest environmental factors. Particular attention has been directed to diet, since the incidence seems to be greater in those whose diet is low in fiber but high in animal fat and protein, perhaps particularly that derived from beef. It is thought that the type of colonic flora associated with such a diet may produce car­cinogens that are in contact with colonic mucosa for longer periods of time due to the prolonged colonic transit times of low-fiber diets. These speculations, and those concerning the possible protective effect of dietary selenium, ascorbic acid, and alpha-tocopherol, await confirmation.

In addition to these possible environmental fac­tors within populations, a number of risk factors are known for the individual . The risk of colorectal carcinoma begins to increase around age 40 and roughly doubles for each suc­ceeding decade. A number of conditions associ­ated with increased mucosal cell turnover may lead to increased risk, e.g., inflammatory bowel disease, especially ulcerative colitis (see Chapter 40), and certain familial polyposis syndromes (to be discussed subsequently). A history of previous cancer or adenoma of the colon, a history of colon cancer in a first-degree relative, and the “family cancer syndrome” (multifocal cancers in other or­gans, especially the female sex organs, as well as the colon) carry increased risk for carcinoma of the colon as well.