Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is an inherited condition. It causes many precancerous growths, called adenomatous polyps, to form in the colon and rectum. Without treatment, at least one of them becomes cancer.

Reported incidence of FAP varies from about 1 in 7,000 to 1 in 22,000 live births. It accounts for about 0.5% of all cases of colorectal cancer.

FAP is caused by a change in the APC gene. The APC protein helps block a signaling pathway that drives cell growth and division. When APC does not work, that brake is lost, and the lining of the colon grows polyps.

FAP is inherited in an autosomal dominant pattern. A person with FAP has a 50% chance of passing the APC variant to each child.

In classic FAP, people may have hundreds to thousands of colon polyps.

Polyps start early. The average age at which they appear is 16 years, with a range of 7 to 36 years. By age 35, about 95% of people with classic FAP have colon polyps.

Without surgery to remove the colon, colorectal cancer is essentially inevitable. The mean age at diagnosis is 39 years, with a range of 34 to 43. About 87% have developed colorectal cancer by age 45, and 93% by age 50, if the colon is not removed.

Those numbers are why prevention in FAP is surgical rather than watchful.

Attenuated FAP (AFAP) is a milder form, but it is not a mild disease.

People with AFAP have fewer polyps, an average of about 30. The formal definition is 100 or fewer colorectal adenomas at age 25 or older. The polyps tend to sit higher up in the colon, further from the rectum.

The lifetime risk of colorectal cancer in AFAP is about 70% by age 80. Cancer typically develops around ages 50 to 55.

The higher position of the polyps matters. A flexible sigmoidoscopy, which only reaches the lower colon, can miss them. Full colonoscopy is needed.

For classic FAP, colonoscopy begins at age 10 to 15 years. For attenuated FAP, it begins in late adolescence. The interval is every one to two years.

Yes, this means scoping children. It also means many families face a first colonoscopy conversation during middle school. Ask the genetics team how your center handles that, and whether a pediatric gastroenterologist is involved.

Prophylactic surgery to remove the colon improves survival in FAP. The question is not usually whether, but when.

Surgery is clearly indicated when there is confirmed or suspected colorectal cancer, or significant symptoms.

Surgery is also considered when there are many adenomas larger than 10 mm, when a polyp shows high-grade dysplasia, or when the polyp burden is so heavy that colonoscopy can no longer survey the colon reliably.

That last reason is easy to overlook. Once a surgeon cannot count or clear the polyps, surveillance stops being surveillance.

Ask which operation is proposed, what happens to bowel function afterwards, and whether any rectum is left behind. If rectum remains, it still needs regular endoscopy for life.

Removing the colon does not end the risk. Polyps also grow in the duodenum, the first part of the small intestine, especially around the ampulla where the bile duct enters.

Duodenal or periampullary adenomas are seen in 50% to 90% of people with FAP. The lifetime risk of cancer at that site is 4% to 12%.

Regular endoscopic surveillance of the duodenum improves survival in FAP.

Upper endoscopy starts at age 20 to 25, or before colon surgery, whichever comes first. The interval then depends on the Spigelman score, which grades how bad the duodenal polyps are:

• Stage 0 to I: every five years.
• Stage II: every three years.
• Stage III to IV: at least once a year.

Ask for your Spigelman stage by name after each upper endoscopy. It determines when you come back.

Desmoid tumors are growths of fibrous tissue. They are not cancer in the usual sense, because they do not spread to distant organs. But they invade locally, and in the abdomen they can wrap around bowel and blood vessels.

They occur in about 10% to 30% of people with FAP. That is more than 800 times the risk in the general population. They often appear after abdominal surgery.

Report persistent abdominal pain, a firm abdominal lump, or bowel obstruction symptoms to a team that knows FAP.

• Osteomas. Harmless bony growths, in about 60% to 80% of people with FAP, often in the jaw or skull.
• CHRPE. Congenital hypertrophy of the retinal pigment epithelium, flat pigmented spots on the retina, in up to 80% of people. They cause no vision problems, and an eye exam can find them.
• Thyroid cancer. Found in 2.6% to 11.8% of people with FAP in prospective studies, with a striking female-to-male ratio of about 80 to 1. Annual thyroid palpation and thyroid ultrasound are recommended.
• Hepatoblastoma. A childhood liver cancer. The risk is 750 to 7,500 times higher than in the general population, but the absolute risk is estimated at less than 2%.
• Brain tumors. About 1% absolute risk, mainly medulloblastoma.
• Dental and skin findings. Extra teeth, dental cysts, and skin cysts are common.

Celecoxib and sulindac have been associated with a decrease in polyp size and number. They do not replace surgery or surveillance. Ask whether either is appropriate for you, and what the cardiovascular and stomach risks are.

Contact your doctor if you have any of these, even between scheduled scopes:

• Blood in the stool, either bright red or very dark.
• A change in bowel habits: diarrhea, constipation, or a feeling that the bowel does not empty completely.
• General abdominal discomfort, such as frequent gas pains, bloating, fullness, or cramps.
• Weight loss for no known reason.
• Fatigue.
• Vomiting.

Go to the emergency department for severe abdominal pain with vomiting and no bowel movement, or for heavy rectal bleeding. Bowel obstruction is a real risk after abdominal surgery and with desmoid tumors.

Every first-degree relative of a person with FAP has a 50% chance of carrying the same APC variant. That includes children, siblings, and parents.

Genetic testing in a family usually starts with the person already affected. Once the exact variant is known, relatives can be tested for that single variant, which is faster and cheaper.

For classic FAP, testing children is standard practice rather than a personal choice, because screening starts at age 10 to 15. Deferring the test does not defer the risk.

• Do I have classic FAP or attenuated FAP, and which APC variant?
• Who owns my colonoscopy schedule, and who owns my upper endoscopy schedule?
• What was my most recent Spigelman stage?
• What is the plan and expected timing for colon surgery?
• Which relatives should be tested, and at what age should children start screening?

• Genetics of Colorectal Cancer (PDQ) Health Professional Version — National Cancer Institute
• Colon Cancer Treatment (PDQ) Patient Version — National Cancer Institute
• Familial Adenomatous Polyposis — MedlinePlus Genetics, National Library of Medicine
• APC-Associated Polyposis Conditions — GeneReviews, National Center for Biotechnology Information