Causes of Colorectal Neoplasia a Model of Cancer Etiology

Abstract

Enormous progress has been made in the understanding of colorectal cancer etiology since this authoritative pronouncement by Professor Willis 45 years ago, yet large gaps in our understanding still remain. The early lead that there is an inherited susceptibility in colorectal neoplasia came from studies of familial polyposis syndromes and later from studies of family cancer syndromes. In the past decade, knowledge of the inherited susceptibility to colorectal neoplasia has moved forward enormously with research in molecular genetics. The early clues that environmental factors are also important in colorectal neoplasia came from several sources, namely from noting the enormous geographic variation in the incidence of colorectal cancer, from migrant studies showing striking changes in the incidence of colorectal cancer with migration, and from some religious and cultural groups showing differences in colorectal cancer incidence in relation to the population in which they live. The various hypotheses of inherited and environmental exposures were being tested in humans by several groups of cancer epidemiologists around the world using a variety of methodologies, as well as by laboratory scientists using experimental models of colorectal cancer. At the same time, the mechanisms of colorectal tumor formation were being examined by many groups in carcinogenesis research, and more recently by molecular genetic studies also.

In most cases of intestinal carcinoma, no previous lesions or causative factors are recognizable. In a small proportion of cases, the disease supervenes on polypi or inflammatory lesions.

Rupert Willis MD, 1950 Professor of Pathology University of Leeds