Familial adenomatous polyposis

Overview

Familial adenomatous polyposis (FAP) is an inherited condition. This means it is passed from parents to their children through genes. FAP is rare, affecting about 1 in 10,000 people.

FAP leads to the development of hundreds to thousands of growths, called polyps, in the colon and rectum. Polyps typically begin to develop during adolescence and increase in number over time. Without treatment, the lifetime likelihood of colorectal cancer approaches 100%, often by age 40.

FAP is caused by a change in the APC gene. This change is called a mutation or a variant. The APC gene typically helps regulate cell growth in the intestinal lining. When this gene is altered, cells can grow out of control. This leads to the formation of many polyps.

These polyps usually grow throughout the colon rather than being limited to one part. In addition to having colorectal polyps, people with FAP may have polyps in other parts of the digestive tract, including the stomach and small intestine. There also is a higher risk of tumors and cancers in other parts of the body.

Variants and related conditions of FAP

Familial adenomatous polyposis (FAP) can vary in how it appears. Differences may include the number of polyps, when they develop and whether the disease affects other parts of the body.

Milder form of FAP

Attenuated familial adenomatous polyposis (AFAP) is a milder form of FAP. It is caused by changes in the APC gene but usually leads to fewer polyps, often fewer than 100. Polyps tend to develop later in life. The likelihood of colorectal cancer remains high, but it is lower than in classic FAP.

Features outside the colon

Some people with FAP have findings outside the colon. In the past, terms such as Gardner syndrome and Turcot syndrome were used to describe these features. Today, they are generally considered part of the same condition rather than separate syndromes. These features may include bone growths, dental changes, soft tissue tumors or tumors of the central nervous system.

Other inherited colorectal cancer conditions

Other genetic conditions can increase the risk of colorectal cancer or cause multiple polyps, but they develop in different ways:

• Lynch syndrome. This condition is caused by changes in a different group of genes. It typically leads to few or no polyps but still increases cancer risk.
• MUTYH-associated polyposis (MAP). Similar to FAP, this condition can cause multiple colon polyps. It is inherited in an autosomal recessive pattern, meaning both copies of the gene must be altered. It may not appear across multiple generations of a family.
• Juvenile polyposis syndrome, Peutz-Jeghers syndrome and Cowden syndrome. These conditions also can cause polyps in the digestive tract. However, the polyps have different features under the microscope and are linked to different genes.

Causes

Familial adenomatous polyposis (FAP) is caused by a change in the APC gene. This change is called a mutation or variant. The gene helps control how cells grow and divide in the lining of the colon.

When the APC gene is working as expected, it helps prevent cells from growing too quickly. When a mutation is present, this control is lost. Cells can grow and divide out of control. This leads to the formation of many polyps.

Over time, some of these polyps can become cancer. The high number of polyps increases the chance that cancer will develop.

FAP is inherited, meaning it is passed from parents to children through genes. A person only needs to inherit one copy of the altered APC gene to develop the condition. Each child of a parent with FAP has a 50% chance of inheriting the condition.

In about 20% of people with FAP, the condition develops without a family history. In these situations, the variant in the APC gene appears for the first time in that individual. This is known as a de novo variant.

Complications

In addition to colon cancer, familial adenomatous polyposis (FAP) can lead to several complications, most of which are related to polyp growth and increased cancer risk in other areas of the body.

Complications may include:

• Small intestine cancer. Polyps can develop in the upper part of the small intestine. This includes the duodenum and the area where the bile and pancreatic ducts enter, called the ampulla. These polyps can become cancerous over time.
• Stomach polyps. Polyps may form in the stomach. Most do not become cancer, but some types may carry a small risk.
• Desmoid tumors. These are noncancerous growths that can develop in the abdomen or other areas. They can grow into nearby tissues and sometimes cause serious issues.
• Other cancers. FAP increases the likelihood of cancers such as thyroid cancer, adrenal gland tumors and cancer of the central nervous system. Less commonly, cancers of the liver or bile duct may occur.

Other features of FAP

FAP also can cause changes in other parts of the body. They include:

• Bone growths, called osteomas.
• Dental changes, which may include extra teeth, called supernumerary teeth; teeth that do not come in as expected, known as impacted teeth; missing teeth; or other changes in tooth development.
• Skin cysts or other soft tissue growths, such as fibromas.
• Changes in the back of the eye, called congenital hypertrophy of the retinal pigment epithelium (CHRPE).

Treatment

Treatment for familial adenomatous polyposis (FAP) focuses on reducing the risk of cancer and managing polyp growth.

Early in the condition, small polyps found during colonoscopy may be taken out. Over time, however, the number of polyps usually increases and becomes too large to manage individually, often by the late teens or early 20s. At that point, surgery is recommended to prevent colorectal cancer.

Surgery also may be needed if a polyp becomes cancerous. In some cases of attenuated familial adenomatous polyposis (AFAP), surgery may be delayed or not needed right away, depending on the number and features of the polyps.

Surgery

Surgery is the main treatment for FAP because of the high likelihood of colorectal cancer. The goal is to remove the at-risk tissue while preserving quality of life.

• Colectomy with ileorectal anastomosis. This surgery removes the colon but keeps the rectum. The small intestine is connected to the rectum. This option may be used when the rectum has fewer polyps and can be managed with ongoing screening.
• Proctocolectomy with ileal pouch-anal anastomosis. This procedure removes both the colon and the rectum. A pouch, often called a J-pouch, is created from the small intestine and connected to the anus to allow stool to pass without creating an opening in the abdomen, called an ostomy.
• Proctocolectomy with ileostomy. This surgery removes the colon and rectum and brings the end of the small intestine to an opening in the abdomen, called an ileostomy. Waste is then collected in a bag outside the body.

The type and timing of surgery depend on the number, size and features of the polyps, as well as individual preferences and overall health.

Medications

You may take medicines to help lessen the number of polyps or slow their growth. These treatments are most often used along with surgery and screening, not as a replacement.

• Nonsteroidal anti-inflammatory drugs (NSAIDs). Medicines such as sulindac or celecoxib may lessen the number and size of polyps. These uses are considered off-label. However, these medicines do not eliminate cancer risk and do not replace surgery.
• Other medicines. Sometimes, additional medicines may be used, especially for related conditions such as desmoid tumors. These may include targeted therapies or other treatments recommended by a specialist.

Treatment of related conditions

Additional treatment may be recommended based on screening results and the features of FAP.

• Duodenal and periampullary polyps. Polyps in the upper small intestine may be taken out using endoscopy or surgery. This can include polyps in the duodenum and the ampulla. Removal may be recommended if the polyps have features that increase the risk of cancer.
• Desmoid tumors. Treatment often begins with medicines, such as NSAIDs or other therapies. More treatments, including chemotherapy or surgery, may be needed if the tumors cause symptoms or continue to grow.
• Osteomas. These noncancerous bone growths may be removed if they cause pain or for cosmetic reasons.

Regular screening

Even after treatment, you need regular screening to monitor for new polyps and related conditions.

• Lower gastrointestinal screening. The remaining rectum or surgically created pouch is regularly checked for new polyps.
• Upper gastrointestinal screening. Endoscopy is used to monitor the stomach and small intestine for polyps.
• Other screening. Additional exams, such as thyroid evaluation or imaging, may be recommended based on individual risk.

Preparing for an appointment

Appointments for familial adenomatous polyposis (FAP) may involve discussion of screening, genetic testing and treatment options. Being prepared can help you get the most from your visit.

What you can do

• Gather family history. Bring information about blood relatives, such as parents, grandparents and siblings, who have had colon polyps, colorectal cancer or other related conditions, including their age at diagnosis if known.
• List symptoms and concerns. Write down any symptoms, even if they do not seem related, along with questions you want to ask.
• Bring test results. If you have had prior colonoscopies, imaging or genetic testing, bring copies of those results if available.
• Make a list of your medicines. Include all prescription and nonprescription medicines, vitamins, and supplements.
• Consider bringing someone with you. A family member or friend can help remember information and provide support.

Questions to ask your doctor

• What tests do you recommend to confirm or monitor FAP?
• How often should I have screening?
• What treatment options are available, and when might surgery be needed?
• Should I consider genetic testing?
• What does this mean for family members?