Familial adenomatous polyposis 23/3/06. By Christina Giles. Reviewed by Jules Harvey and Robin Phillips Familial adenomatous polyposis is an inherited cancer syndrome that predisposes patients to early-onset colorectal cancer, among other cancers.

Familial adenomatous polyposis (FAP) is very rare and affects 1 in 7000 people, causing less than 1 per cent of all colorectal cancer cases. The average age for the onset of colorectal cancer in FAP patients is 39 years, and untreated, everyone with FAP will develop colorectal cancer.

Genetics

FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. FAP is inherited in a dominant fashion, so that an affected patient has a 50 per cent chance of passing on the defective gene. All FAP patients are born with 1 defective and 1 normal copy of APC.

People with FAP develop numerous adenomatous colorectal polyps (protruding, non-cancerous growths in the colon or rectum) in their teens and twenties. The average age for the onset of polyps is 16. The polyps themselves are not cancerous, but because there are so many, there is a high chance that some will undergo a mutation in the normal copy of the APC gene, and trigger the development of cancer.

APC is a tumour suppressor gene. One of the many roles of APC is regulating cell replication. Most mutations in the APC gene result in a short, non-functioning protein that disrupts the balance of cell proliferation and cell death.

Hundreds of APC mutations have been identified. Research has shown that there is a link between the site of the APC mutation and the number and site of polyps that as patient will have. This is known as the 'genotype-phenotype' correlation.

Mutated APC has been linked to chromosomal instability, where aneuploidy (an abnormal number of chromosomes) is seen in cells. Chromosomal instability is thought to occur in 85 per cent of all colorectal cancer cases. The other main genetic pathway for colorectal cancer is microsatellite instability (MIS), seen in Hereditary non-polyposis colorectal cancer (HNPCC).

Background: Hereditary non-polyposis colorectal cancer

A disorder called attenuated FAP (AFAP) exists. Less is known about AFAP, but patients have fewer polyps than classical FAP patients. In AFAP, the onset of colorectal cancer is ten to 20 years later than in classical FAP and does not necessarily affect every patient, as it does in FAP.

Symptoms

FAP might be asymptomatic, especially if the patient is being seen at a young age because of a positive family history.

Patients may present with rectal bleeding, tummy pain, bony growths (benign bone tumours called osteomas) or symptoms related to cancer.

Diagnosis

FAP is suspected after a thorough history and examination. To be diagnosed with FAP, a patient needs to have more than 100 colorectal polyps, or fewer plus a relative with confirmed FAP. Patients with an APC mutation or multiple polyps or one affected first-degree relative should be examined by flexible sigmoidoscopy (a bendy camera inserted up the bottom to look at the rectum and some of the large bowel) annually from their mid-teens. Genetic testing is also used to help diagnose FAP.

Endoscopic (camera test) surveillance of the upper small intestine is also recommended as patients also develop polyps there.

Treatment

As colorectal cancer is a certainty in these patients, most patients opt for elective removal of their colon during their late teens or twenties, before cancer develops. They still require life long follow-up though for other cancers. (See Colorectal cancer for details on the treatment of this cancer.)

Christina Giles is a freelance writer based in London. Dr Jules Harvey and Professor Robin Phillips are at the Colorectal Cancer Research Unit, St Mark's Hospital, Harrow.

Links

Cancer Research UK: About Cancer

CancerBACUP: Cancer of the large bowel

Beating Bowel Cancer