Understanding the Genetics of Familial Adenomatous Polyposis (FAP)

Familial Adenomatous Polyposis (FAP) is a rare, inherited condition that affects the gastrointestinal tract. Diagnosis is made when 100 or more adenomatous colonic polyps develop. It is caused by a defect in the gene called the adenomatous polyposis coli (APC) gene. It is mostly inherited directly from a parent, but there is a 25 to 30% chance that it develops due to a genetic mutation.

FAP causes polyps to form in the large intestine (colon) and rectum, it can sometimes occur in the upper part of the small intestine (duodenum). These hundreds of polyps (extra tissues) are harmless, but overtime can become cancerous if untreated, usually by the time the patient is in their 40s.

These polyps can be removed by surgery and are usually managed with careful monitoring and by removing polyps regularly.

Types of Familial Adenomatous Polyposis

There are different subtypes of FAP that vary in their clinical features, these include:

Classic FAP: Classical FAP is diagnosed clinically when an individual has 100 or more adenomatous colorectal polyps.  Surgery to remove the colon is often the most effective way to treat polyps and reduce the risk of colorectal cancer.

Attenuated FAP (AFAP): AFAP is often associated with multiple adenomatous colorectal polyps, i.e., 20 to 100 polyps in number. These patients develop polyps regularly during their lifetime and need continuous monitoring and removal of polyps. It is necessary that the polyps are removed to avoid turning them into cancer. It is not clearly understood if families with AFAP have similar risk factors as classic FAP families.

Gardner syndrome:

People with this variant of FAP develop multiple adenomatous colon polyps, along with some tumours that develop on the outside of gastrointestinal organs, which include:

  • Epidermoid cysts, which are lumps in or under the skin
  • Fibromas, which are fibrous tumours
  • Desmoid tumours – non-cancerous fibrous tumours
    that can develop anywhere in the body
  • Osteomas, which are lumps in or on bone

Turcot syndrome:

It is considered to be a variant of either FAP or Lynch syndrome. People with Turcot syndrome have multiple adenomatous colon polyps, an increased risk of developing colorectal cancer, and an increased risk of brain tumours. The type of brain tumour generally depends on whether the Turcot syndrome is more like Lynch syndrome or more like FAP.

The two common types of brain tumours in Turcot syndrome are Glioblastoma (which is widespread in families with Lynch syndrome symptoms) and Medulloblastoma (children and families with FAP traits are mostly affected).FAP AND AFAP are uncommon, whereas, Gardner syndrome and Turcot syndrome are both considered to be rare.

Diagnosis of FAP and its subtypes

FAP is typically found when your doctor finds many colorectal polyps, rather than by the results of a laboratory test. However, blood tests are available to look for disruptive changes in the APC gene and/or MUTYH gene if FAP or the subtypes are suspected.

Diagnosis would look like this:

  • FAP is diagnosed when a person has more than 100 adenomatous colon polyps.
  • AFAP is diagnosed when a person has more than 20 but fewer than 100 polyps.
  • Gardner syndrome is diagnosed when a person has multiple adenomatous colon polyps and/or colorectal cancer along with some of the non-cancerous features.
  • Turcot syndrome is diagnosed when a person has multiple adenomatous colon polyps and/or colorectal cancer, along with either a glioblastoma or medulloblastoma brain tumour.
Other diagnostic procedures include:
  • Digital Rectal Exam
  • Fecal Occult Blood Test
  • Flexible Sigmoidoscopy
  • Colonoscopy
  • Barium Enema
  • Genetic testing is available for FAP as well as other hereditary colorectal conditions. The gene mutation can be identified with a quick blood test.

Estimated Cancer Risks Associated with FAP

  • Colorectal cancer, up to 100% if polyps not removed
  • Desmoid tumour, 10% to 20%
  • Small bowel (intestines), 4% to 12%
  • Pancreatic/ampullary cancer, 2%
  • Papillary thyroid cancer, 2% to 25%
  • Hepatoblastoma, 1.5%
  • Brain or central nervous system tumour, less than 1%
  • Stomach cancer, 5%
  • Bile duct cancer, slightly increased risk
  • Adrenal gland cancer, slightly increased risk

The cancer risk for people with Turcot syndrome depends on whether it resembles Lynch syndrome or FAP.

Cancer risk in FAP and AFAP can be reduced by removing colorectal and duodenal polyps. Studies are underway to see if drugs are effective in reducing the risk of these cancers.

Screening Options for FAP

Following screening is recommended for people with FAP. It is important to discuss with your doctor prior taking any decision.

Sigmoidoscopy or colonoscopy: It must be done every 1 to 2 years starting at age 10 to 12 for people with FAP. This is particular for children. Individuals with AFAP should undergo colonoscopy beginning at age 18 to 20.

Yearly colonoscopy should be done, until colectomy is planned.

Surveillance after colon surgery with sigmoidoscopy, for every 6 to 12 months for any rectal tissue remains;
every 1 to 4 years to check if all rectal tissue is removed.

Computed tomography (CT) scan or magnetic resonance imaging (MRI) recommended if the person has personal or family history of desmoid tumors.

Upper endoscopy (EGD) should be done once colorectal polyps are found by the age of 25. This screening looks for any presence of duodenal polyps.

Ultrasound used to scan thyroid gland for monitoring thyroid cancer at age 25 to 30.
The cancer risk for people with Turcot syndrome depends on whether it resembles Lynch syndrome or FAP.

Cancer risk in FAP and AFAP can be reduced by removing colorectal and duodenal polyps. Studies are underway to see if drugs are effective in reducing the risk of these cancers.
Screening options for Gardner syndrome are similar with those of FAP, but with addition of regular skin examinations by a dermatologist. The screening options for Turcot syndrome are similar to those for Lynch syndrome or FAP, with the addition of screening for a brain tumor.

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Understanding the Genetics of Familial Adenomatous Polyposis (FAP)