Hereditary Colorectal Cancer Syndromes: Familial Adenomatous Polyposis (FAP) 

Familial adenomatous polyposis (FAP) is a rare condition where a person has a large number of noncancer (benign) polyps in the colon and rectum. It affects men and women equally. 

The name Gardner syndrome is sometimes used for a subtype of FAP. People with this condition also have growths outside the colon. These can include benign bony growths (osteomas), cysts under the skin, and soft tissue tumors.

In its classic form, FAP:

• Causes hundreds to thousands of benign polyps to grow in the colon and rectum. (This is called polyposis.) These are described as having a dense carpet-like appearance when seen on colonoscopy or sigmoidoscopy.

  • These polyps start to develop at a young age, often in the mid-teens.

  • If not treated, a person with FAP has a 100% risk of developing colorectal cancer, often by age 40.

• Is most often inherited from a mother or father with the disorder. But about 1 in 3 people with FAP have no family history of it.

• Leads to an increased risk of many other health problems, such as:

  • Polyps in the upper gastrointestinal tract

  • Osteomas

  • Skin lesions (epidermoid cysts)

  • Locally invasive tumors that grow fast and can be life-threatening (desmoid tumors)

  • Congenital hypertrophy of retinal pigment

  • Dental abnormalities, such as extra or missing teeth

• Is linked to an increased risk of thyroid, adrenal gland, small bowel, pancreatic, bile duct, and stomach cancers. It's also linked to a higher risk of brain tumors and a childhood liver tumor (hepatoblastoma).

Changes (mutations) in a gene called APC cause most cases of FAP. The APC gene usually controls cell growth and cell death. Everyone has 2 APC genes. When a person has a mutated APC gene, their risk of having polyps and their risk of cancer increases. 

Because FAP starts at an early age, cancer screening often starts in childhood. Genetic testing of children at risk is also advised. A child whose parent has FAP has a 50% chance of inheriting it. If the child doesn't have the defective gene, they may not need tests, such as sigmoidoscopy or colonoscopy.

What are the variations in the APC gene?

Hundreds of mutations have been found all over the APC gene. Some families with APC mutations have different symptoms than others. Where a mutation is in the gene gives some information about the types of FAP-linked health problems a person will have. For instance, mutations in certain parts of the gene are linked to a higher rate of desmoid tumors, osteomas, and epidermoid cysts. Where the mutation is found also gives some information about how many polyps a person will have.

What is attenuated FAP?

People with attenuated familial adenomatous polyposis (AFAP) develop 20 to 100 polyps. The risk of having colon cancer is still higher. But the average age of diagnosis is older (about age 55) than in the classic form of FAP. Some of the other health problems linked to classic FAP also happen with AFAP. But congenital hypertrophy of the retinal pigment epithelium is rare.

Mutations in 3 certain parts of the APC gene have been linked to AFAP. The number of polyps developed and the risk of other ways FAP shows up will vary, depending on which part has the mutation.

What is a I1307K mutation?

One APC mutation, called I1307K, is present in about 6% of the American Ashkenazi Jewish population. This mutation is linked to a 10% to 20% risk of colorectal cancer (slightly more than double the average risk for the general population). But people with this mutation don't have the classic carpet of polyps in the colon that's seen in FAP.