Evolution of hereditary bowel cancer.

Familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) are both inherited as autosomal dominant conditions in which the mutation gives rise to a tendency to produce precancerous adenomas. However these two forms of hereditary bowel cancer show important differences at the clinical, pathological and molecular genetic levels. It is argued that the first tissue manifestation of FAP is the unicryptal adenoma. The existence of a preceding field change characterised by diffuse hyperproliferation and various altered phenotypes does not stand up to critical scrutiny. The processes of neoplastic evolution in FAP and HNPCC are compared in detail. It is suggested that an understanding of the function of the FAP and HNPCC genes will lead to the development of cancer prevention strategies aimed at blocking the earliest stages of neoplastic development.