Preclinical Detection of Familial Adenomatous Polyposis: Fact or Fancy?

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Abstract
Familial adenomatous polyposis (FAP), formerly called familial polyposis coli, is characterized by an autosomal dominant mode of inheritance and by the presence of at least 100 adenomatous polyps in the large bowel. The current clinical approach with regard to relatives at risk for FAP includes sigmoidoscopy at regular intervals to detect the polyps and, eventually, the carcinomas in their early stages of development. Once the diagnosis is made, the large bowel is removed to prevent the otherwise inevitable development of colorectal cancer and early death. All first-degree relatives of the patients have an a priori chance of 50% of developing the disease. However, before the onset of the phenotypic expression of the disease it is impossible to discriminate the FAP-gene carriers from the non-carriers. The gene responsible for FAP was recently localized on the long arm of chromosome 5 by using polymorphic DNA markers. Subsequent linkage studies with different polymorphic DNA markers led to the possibility of identifying individuals at risk for the disease with at least a 90% reliability. This development is of great clinical importance because it eliminates unnecessary endoscopies and anxiety in individuals who will not be affected, and it could provide the secondary prevention of colorectal cancer in the carriers of the gene more directly. The identification of the basic genetic defect and thus the prediction of the risk status with 100% certainty appears to be just a matter of time.