Familial adenomatous polyposis (FAP) is an inherited condition in which numerous polyps form mainly in the lining (epithelium) of the large intestine (also called the colon). While these polyps start out benign, malignant transformation into colon cancer occurs when left untreated.
Signs and symptoms
From early teens onward, hundreds to thousands of polyps develop. These may bleed, leading to blood in the stool or anaemia. If malignancy develops, this may present with weight loss, altered bowel habit, or even metastasis to the liver causing yellow skin (jaundice). Those with the genetic defect for FAP may also be predisposed to other malignancies, of the small intestine (duodenum) and stomach. Rarer tumours include connective tissue (Desmoid) tumours of the abdomen (Desmoid). Even rarer tumours include pigmented lesions of the retina (“CHRPE – congenital hypertrophy of the retinal pigment epithelium”), jaw cysts, sebaceous cysts, and osteomata (benign bone tumours). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed Gardner’s syndrome.
Diagnosis and cancer prevention
Making the diagnosis of FAP before the development of colon cancer or duodenal cancer is important. Colonoscopy and gastroscopy are considered the diagnostic test of choice as they can provide not only a quantification of polyps but also endoscopic removal of polyps allowing for histologic diagnosis.
Once the diagnosis of FAP is made, close colonoscopic surveillance with polypectomy is required. Prophylactic total proctocolectomy with formation of a J-Pouch is indicated if more than a hundred polyps are present, if there are severely dysplastic polyps, or if multiple polyps larger than 1 cm are present. When a partial colectomy is performed, colonoscopic surveillance of the remaining colon is necessary as the individual still carries significant risk of developing colon cancer.
Genetic testing
Genetic testing provides the ultimate diagnosis in 95% of cases; genetic counselling is usually needed in families where FAP has been diagnosed.
Genetic mutation
APC is a tumour suppressor gene, acting as a “gatekeeper” to prevent development of tumours. Mutation of APC also occurs commonly in incident cases of colorectal carcinoma, emphasizing its importance in this form of cancer.
Although the polyps are at first benign, the first step of the two-hit hypothesis has already taken place: the inherited APC mutation. Often, the remaining “normal” allele is mutated or deleted, accelerating generation of polyps. Further mutations (e.g. in kras, DCC or p53 genes) to APC-mutated cells are much more likely to lead to cancer than they would in non-mutated epithelial cells.
Genetic registries
Because of the genetic nature of FAP, polyposis registries have been developed around the world. The purpose of these registries is to increase knowledge about the transmissibility of FAP, but also to document, track, and notify family members of affected individuals.
