What Is Familial Adenomatous Polyposis?

What Is Familial Adenomatous Polyposis?

Familial adenomatous polyposis (Familial Adenomatous Polyposis = FAP) is an inherited genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps.

What is an adenomatous polyp?

An adenomatous polyp is an area where the normal cells lining a person's colon form a mass inside the intestinal tract. In people with FAP, the average age at which polyps form is around 10. Most people with FAP develop multiple colon polyps by age 35. If FAP is not recognized and treated, the likelihood of developing colorectal cancer is very high.

Below, you can see a photograph of the inner surface of a surgically removed section of colon containing a dense collection of adenomatous polyps:

People with FAP have an increased risk of cancers in other organs, such as the stomach, small intestine, pancreas, and bile ducts. Children with FAP have an increased risk of hepatoblastoma, a rare type of liver cancer. Some people may also develop desmoid tumors / desmoid fibromatosis, a locally aggressive, noncancerous type of tumor, and a rare type of brain tumor called medulloblastoma. The risk of papillary thyroid cancer is also increased.

What are the symptoms of familial adenomatous polyposis (FAP)?

Not all signs and symptoms of FAP are related to cancer. Some additional features of FAP include:

• Osteomas, which are noncancerous bone growths (usually found in the jaw)
• Extra, missing, or unerupted teeth
• Congenital hypertrophy of the retinal pigment epithelium (CHRPE). This is an eye condition present at birth that does not affect vision, but an ophthalmologist can see it during an examination with a special instrument called an ophthalmoscope.
• Noncancerous skin changes, such as epidermoid cysts and fibromas
• Kidney masses

Are there subtypes of FAP?

There are subtypes of FAP that can vary in their clinical features, including the following:

• Classic FAP is generally characterized by more than 100 colorectal polyps, as described above. Surgically removing part of the colon is the most effective way to manage the polyps and reduce the risk of colorectal cancer.
• Attenuated (Attenuated) FAP is usually associated with numerous adenomatous colorectal polyps, such as 20 to 100 polyps. People with attenuated FAP generally continue to develop adenomatous colon polyps throughout their lives and have an increased risk of colorectal cancer if the polyps are not removed. People with attenuated FAP tend to develop polyps later in life than those with classic FAP. It has not yet been determined whether families with attenuated FAP have the same risk of other cancers and other features associated with classic FAP as families with classic FAP.
• Gardner syndrome, a variant of FAP, causes people to develop numerous adenomatous colon polyps, as in FAP. In addition, however, other tumors may develop outside the organs of the digestive system. These tumors include:
  • Epidermoid cysts (lumps in or under the skin)
  • Fibromas
  • Desmoid tumors (noncancerous fibrous tumors that can develop anywhere in the body)
  • Osteomas (lumps in or on bone)
• Turcot syndrome is considered a variant of FAP or Lynch syndrome rather than a separate genetic condition in its own right. People with Turcot syndrome have multiple adenomatous colon polyps and an increased risk of colorectal cancers and brain tumors. The type of brain tumor generally depends on whether Turcot syndrome more closely resembles Lynch syndrome or FAP. The two most common types of brain tumors in Turcot syndrome are:
  • Glioblastoma: This type of brain tumor is an aggressive form of astrocytoma commonly found in families with features of Lynch syndrome.
  • Medulloblastoma: This type of brain tumor begins in the cerebellum at the back of the brain. Medulloblastoma occurs most often in children and is generally found in families with features of FAP.

What causes classic FAP and its subtypes?

FAP is passed down from generation to generation in a family. Present at birth, APC gene mutations (genetic changes) are linked to FAP, attenuated FAP, Gardner syndrome, and Turcot syndrome.

Such a change in a gene may also be called a genetic mutation, a gene alteration, a pathogenic germline (inherited) alteration, or a disruptive gene change.

APC stands for adenomatous polyposis coli. A person with a genetic change that disrupts the function of the APC gene has an increased lifetime risk of developing multiple colorectal polyps (dozens or hundreds), colorectal cancer, and/or other cancers of the digestive system.

Not everyone with FAP has a family history of FAP. One in three people with FAP develops a de novo (meaning "new") germline (inherited) mutation in APC.

Not everyone with colorectal polyposis has FAP. Some people have been found to carry two mutations in the MUTYH gene (also known as the MYH gene), associated with a condition called MUTYH-associated polyposis (MAP). Individuals with FAP and MAP who have colorectal polyps are classified as the "adenoma or adenomatous" type. However, individuals with colorectal polyposis with "hamartoma, inflammatory, or juvenile" types of polyps may have alterations in different genes, as in cases of juvenile polyposis.

To detect genetic mutations in the APC gene or MUTYH gene in people with FAP or attenuated FAP, a special genetic test can be performed. If a specific gene mutation that disrupts the gene's function is found, other family members are also screened, and they are diagnosed with FAP or attenuated FAP when the same gene mutation is detected.

How are classic FAP and its subtypes passed on to later generations?

Normally, each cell has 2 copies of a gene, one inherited from the mother and one from the father. FAP with an APC gene mutation known to disrupt gene function follows an autosomal dominant inheritance pattern, and a mutation in only a single copy of the gene is sufficient for it to occur. This means that a parent with a gene mutation can pass a copy of either their normal gene or their mutated gene to their child. Therefore, a child with a parent who has the mutation has a 50% chance of inheriting it. A brother, sister, or parent of a person with the mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (no mutation is found in their test results), the risk to siblings is significantly reduced, although their risk may still be higher than average.

There are options for people who have an inherited cancer syndrome and wish to have children. Preimplantation genetic diagnosis (PGT) is a medical procedure performed in conjunction with in vitro fertilization (IVF) that may allow a child to be born without passing on a specific gene mutation. A woman's eggs are retrieved and fertilized in a laboratory. When the embryos reach a certain size (approximately 8 cells), 1 cell is removed and tested for the inherited condition in question. The parents can then choose to transfer embryos without the mutation into the woman's uterus. PGT has been used for more than twenty years to prevent various inherited cancer predisposition syndromes. However, it is a complex procedure, and financial, physical, and emotional factors should be considered before starting PGT.

How common are classic FAP and its subtypes?

FAP and attenuated FAP are rare. Estimates of the number of people with FAP range from one in 22,000 to one in 7,000. Approximately 30% of people with FAP have no family history of FAP and are the first person affected by the condition in their family.

Most colorectal cancers are sporadic, meaning they occur by chance and are unrelated to FAP or other inherited syndromes. Less than 1% of all colorectal cancers are thought to be due to FAP.

Gardner syndrome and Turcot syndrome are both known to be rare.

How are classic FAP and its subtypes diagnosed?

Classic FAP is a clinical diagnosis. This means that the condition is diagnosed when many colorectal polyps are found rather than on the basis of laboratory test results. A person with more than 100 adenomatous colon polyps is considered to have FAP.

Attenuated FAP is suspected when a person has a history of more than 20 but fewer than 100 adenomatous colon polyps.

Gardner syndrome is suspected when a person has multiple adenomatous colon polyps and/or colorectal cancer along with some of the noncancerous features listed above.

Turcot syndrome is suspected when a person has multiple adenomatous colon polyps and/or colorectal cancer along with a glioblastoma or medulloblastoma brain tumor.

If FAP or one of its subtypes is suspected, genetic blood tests are available to look for disruptive changes in the APC gene and/or MUTYH gene. If an APC gene mutation is found, other family members can be diagnosed with FAP or a subtype if they are tested and found to have the same gene mutation.

Which cancer risks do classic FAP and its subtypes increase, and by how much?

• Colorectal cancer, up to 100% if polyps are not removed
• Desmoid tumor, 10% to 20%
• Small intestine cancer, 4% to 12%
• Pancreatic / ampullary cancer, 2%
• Papillary thyroid cancer, 2% to 25%
• Hepatoblastoma, 1.5%
• Brain or central nervous system tumor, less than 1%
• Stomach cancer, 5%
• Bile duct cancer, low risk
• Adrenal gland cancer, low risk

For people with Turcot syndrome, cancer risk depends on whether it appears more similar to Lynch syndrome or FAP. Visit the Lynch syndrome section of our website for cancer risks and other features.

What are the screening options for classic FAP and its subtypes?

ASCO recommends the following screening for people with FAP. Since each individual is different, you should discuss these options with your healthcare team.

• Sigmoidoscopy or colonoscopy every 1-2 years, beginning at ages 10 to 12 for people with FAP, and colonoscopy beginning at ages 18 to 20 for people with attenuated FAP.
• After polyps are detected, annual colonoscopy should be performed until a colectomy (removal of part of the colon) is planned. There are different types of colon surgery for people with FAP and attenuated FAP. People with classic FAP, because of their high number of polyps and high risk of colorectal cancer, total colectomy (surgical removal of the entire colon). This is a major operation, and possible side effects may require a colostomy (bringing the colon out to an external opening). Talk to your healthcare team about what may happen during and after surgery.
• After colon surgery, doctors monitor the patient's lower intestinal tract with sigmoidoscopy, and this monitoring should continue at regular intervals depending on the type of surgery (every 6 to 12 months if colon tissue remains after surgery, or every 1 to 4 years if all colon tissue has been removed and there is a small-intestinal pouch).
• Upper endoscopy should be performed when colorectal polyps are found or by age 25. This is important for monitoring polyps in the duodenum. If duodenal polyps are not removed, the person's risk of duodenal or ampullary cancer increases.
• Thyroid ultrasound to monitor for thyroid cancer should begin at ages 25-30.
• A computed tomography (CT) scan or magnetic resonance imaging (MRI) may be recommended if a person has a personal or family history of desmoid tumors.

Screening options for Gardner syndrome are thought to be similar to those for classic FAP. In addition, regular skin examinations should be performed by a dermatologist, a doctor specializing in skin diseases. Screening options for Turcot syndrome are thought to be similar to those for Lynch syndrome or FAP, with the addition of brain tumor screening.

Screening options may change over time as new technologies are developed and more is learned about FAP and its subtypes. You can discuss appropriate screening tests with your healthcare team.

Are there other ways to reduce the cancer risks associated with FAP?

The cancer risk in FAP and attenuated FAP can be reduced by removing colorectal and duodenal polyps. Studies are ongoing to determine whether medications may be effective in reducing cancer risks. A recent clinical trial found that a combination of two drugs, sulindac and erlotinib, reduced the number of colorectal and duodenal polyps. Although this is promising, this treatment is not currently standard care because more research is needed to determine its long-term results.

Questions to ask your healthcare team about FAP

If you are concerned about your risk of colorectal cancer or other cancers, talk to your healthcare team. It may help to bring someone with you to your appointments to take notes. You can ask your healthcare team the following questions:

• What is my risk of developing colorectal cancer?
• How many colon polyps do I have in total?
• What types of colon polyps do I have? (The two most common types are hyperplastic and adenomatous.)
• What is my risk of developing another type of cancer?
• What can I do to reduce my cancer risk?
• What are my options for cancer screening and prevention?

If you are concerned about your family history and think that your family may have FAP or one of its subtypes, you can ask the following questions:

• Does my family history increase my risk of colorectal cancer?
• Should I see a genetic counselor?
• Should I consider genetic testing?