Molecular genetic studies of the adenoma-carcinoma sequence.

During the past decade, a great deal of progress has been made toward identifying some of the genetic alterations that underlie human cancer development in general, and colorectal cancer in particular. It is now clear that mutations in both oncogenes and tumor suppressor genes have an important role in the process. However, much work lies ahead before a complete understanding of the pathogenesis of colorectal tumors will be obtained. It seems reasonable to predict that additional oncogenes and tumor suppressor genes with important roles in colorectal cancer remain to be identified. Characterization of the function of these genes in normal and neoplastic cell growth will be crucial. Unfortunately, we know little about the functions of the oncogenes and tumor suppressor genes already implicated in colorectal cancer. Undoubtedly, it will be crucial to understand the role of environmental and dietary influences on the nature and rate of mutations in colorectal tumors. Little is known about the relative significance of each of the various inherited and somatic mutations to the cancer phenotype. Moreover, although some preliminary studies have suggested possible clinical applications of the genetic studies to improved diagnosis and management of patients at risk of and harboring colorectal cancer, the scope and significance of the observations thus far are limited. Nevertheless, an optimistic view is that future molecular genetic studies not only will yield insights into the molecular basis of colorectal cancer, but also will improve the care of patients with colorectal tumors.