Knowledge of the adenomatous polyposis coli gene and its clinical application

Familial adenomatous polyposis (FAP) is one of the most clearly defined and well understood of the inherited colorectal cancer syndromes. It is an autosomal dominant condition with high (> 90%) penetrance. Clinically, it is characterized by multiple (> 100) adenomatous polyps in the colon and rectum; variant features in addition to the colonic polyps may include polyps in the upper gastrointestinal tract and other extracolonic manifestations. Since the risk of colorectal cancer in untreated FAP is virtually 100%, screening and intervention for at-risk persons has consisted of annual colon examinations by endoscopy beginning around puberty. The objective of this regimen is early detection of colonic polyps in those who have FAP, followed by preventive colectomy. Because of recent findings that most cases of FAP are due to mutations of the adenomatous polyposis coli gene at chromosome 5q21, genetic testing will probably be incorporated as the first step in the management of individuals at risk for this condition, and screening regimens can be modified. Genetic counselling about the consequences of presymptomatic gene testing is an important component of this process.