Familial Adenomatous Polyposis and the APC gene
Familial Adenomatous Polyposis (FAP), as the name suggests, causes polyps. It affects 1 in 7,000 to 1 in 22,000 people.
In the classic form, 100s to 1000s of adenoma develop in the colon (bowel). These polyps start appearing in childhood and left untreated these polyps almost always become cancerous. The classical form is associated with a phenotype that includes desmoids, cysts in the jaw (osteomas), changes in the eye (CHRPE) and polyps elsewhere in the gastrointestinal tract.
There is also a milder form called attenuated FAP (AFAP). Here, 10s to 100s of polyps develop. The polyps usually appear in the 20s or older and there are usually no other signs or symptoms.
Adenomatous polyps are the most common kind of polyp found in the bowel. If you have had a few polyps removed in your 50s or 60s, don't panic! That is quite common and is why bowel cancer screening starts at 50 in the general population. However, if you have had more than 20 or if the polyps were detected in your 20s or 30s, it could be FAP or attenuated FAP.
Before it was know that inherited mutations in the APC gene were responsible for FAP, Familial Adenomatous Polyposis syndrome was known by other names, based on the clinical features.
Gardner syndrome is a clinical syndrome used to describes families with multiple bowel polyps (adenomas of the colon) and skin lumps such as epidermoid cysts or lipomas, desmoids (tumour of the connective tissues) and osteomas (benign bone growths, often found in the jaw). It's an old term and no longer used. Gardner syndrome also applied to families with Lynch syndrome who had sebaceous adenocarcinomas of the skin.
Turcot syndrome is a clinical syndrome used to describe families with multiple bowel polyps (adenomas of the colon) and brain tumours. When the genetic cause is an APC mutation, such as in Familial Adenomatous Polyposis syndrome, the brain tumours are usually medulloblastoma. Turcot syndrome also applied to families with Lynch syndrome but in these families the brain tumours were usually glioblastoma.A particular mutation in the APC gene, written APC c.3920T>A p.(Ile1307Lys), is common in people of Ashkenazi Jewish descent. Rather than switching on the APC gene and causing multiple polyps to grow, this mutation increases the chance that more mistakes will occur in the APC gene itself in bowel cells over time (somatic mutations). It occurs in 6 to 11% of individuals with Ashkenazi heritage. In this population this mutation has been shown to increase the risk of colorectal cancer. Guidelines recommend starting bowel cancer screening with faecal occult blood testing (FOBT) at age 40 and commencing colonoscopy screening every 5 years from age 50, although this may change with the particular family history. Thyroid cancer is not common in individuals with FAP. However, when it does occur, it's usually a rare type called a cribriform-morular variant of papillary thyroid cancer. Germline genetic testing is recommended for everyone who has this rare kind of papillary thyroid cancer.
Management of Familial Adenomatous Polyposis
Screening starts at a young age in FAP. That is why genetic testing is performed in children. The polyps can occur at a very young age and these polyps can become cancer. In classical FAP screening starts at age 10 or 12 with a flexible sigmoidoscopy or colonoscopy performed every year. For attenuated FAP, screening starts at age 18 and may be done every 2 to 3 years until polyps are detected.
Colectomy (surgical removal of the colon) is required when polyp load becomes to high to manage. This is usually around age 18 in classical FAP.
Because the polyps can also occur elsewhere in the digestive tract, screening of the stomach and beginning of the small intestine with an endoscopy is required. This starts at age 25.
There is no evidence that screening for the other cancers or growths, including hepatoblastoma, thyroid cancer or desmoids is helpful or saves lives.
There is a 50% chance of a person who carries a germline APC mutation, whether male or female, passing the mutation to their son or daughter. If a mutation is identified, then predictive testing is available for blood relatives.
Does this sound like you or your family? Has an APC mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.
These links may be useful
- We haven't found a specific Australian Support Group for this syndrome yet. However, FAP Gene Support Group is based in the UK and has good resources
- The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines
- The US National Library of Medicine website has more information about this syndrome.