Adenomatous Polyposis Coli

Adenomatous polyposis coli is a rare, inherited condition that causes hundreds to thousands of growths called polyps to develop in the large intestine, creating a nearly certain risk of cancer by middle age if left untreated.

Table of contents

• What Is Adenomatous Polyposis Coli?
• Different Forms of the Condition
• What Causes This Condition
• Signs and Symptoms
• Risk of Cancer
• How the Condition Is Diagnosed
• Treatment and Management
• Ongoing Monitoring

What Is Adenomatous Polyposis Coli?

Adenomatous polyposis coli, more commonly known as familial adenomatous polyposis or FAP, is a rare inherited disorder that affects the large intestine (colon) and rectum. People with this condition develop many abnormal growths called polyps in the lining of their colon and rectum^[1]. While polyps are not cancer, certain types can change into cancer over time.

Familial adenomatous polyposis, FAP

The condition is caused by a defect in a gene called the adenomatous polyposis coli (APC) gene^[1]. This gene normally helps control cell growth in the body. When it is damaged, cells in the colon grow out of control, forming numerous polyps. The condition affects about 1 in 8,000 to 1 in 8,500 people^[2][5].

• Colon (large intestine)
• Rectum
• Duodenum (upper part of small intestine)
• Stomach

Different Forms of the Condition

There are several forms of familial adenomatous polyposis, which differ in how many polyps develop and when they appear.

The classic form is the most severe type. People with classic FAP develop hundreds to thousands of polyps in their colon and rectum, usually starting in their mid-teens^[1]. By age 35, about 95 percent of people with classic FAP will have developed these polyps^[5]. More than 100 polyps are typically present in this form^[2].

The attenuated form, called attenuated familial adenomatous polyposis (AFAP), is less severe. People with AFAP develop fewer polyps, usually an average of 30, and these polyps appear later in life, typically in early to mid-adulthood^[1][5]. With AFAP, polyps often develop somewhere between 20 and 100 in number^[2].

Some people also have related conditions that include additional features beyond colon polyps. Gardner syndrome involves over a hundred colon polyps along with other types of tumors in different parts of the body^[2]. Turcot syndrome involves multiple colon polyps as well as one cancerous brain tumor^[2].

What Causes This Condition

Familial adenomatous polyposis is caused by changes, called mutations, in the APC gene. This gene provides instructions for making a protein that acts as a tumor suppressor, which means it keeps cells from growing and dividing too quickly or in an uncontrolled way^[5].

Most people inherit the gene mutation from a parent. However, in about 25 to 30 percent of cases, the genetic mutation occurs spontaneously, meaning it happens for the first time in that person without being passed down from a parent^[1][4].

When the APC gene is mutated, it cannot properly control cell growth. This leads to the development of numerous polyps in the colon and rectum. Over time, one or more of these polyps will likely develop into cancer if not treated^[5].

The condition follows an autosomal dominant pattern of inheritance^[4]. This means that if one parent has the condition, each of their children has a 50 percent chance of inheriting the genetic mutation. Your risk is higher if you have a parent, child, brother or sister with the condition^[1].

Signs and Symptoms

The main sign of familial adenomatous polyposis is the development of hundreds or even thousands of polyps in the colon and rectum^[1]. These polyps usually begin to appear by the mid-teenage years in classic FAP, though they may not cause symptoms right away.

When symptoms do occur, they may include rectal bleeding, which is often the first noticeable sign^[2]. Abdominal pain can develop due to the presence of multiple polyps in the colon. Some people experience chronic or frequent diarrhea as a result of the polyps affecting normal colon function^[2].

Besides colon polyps, people with FAP may develop other abnormal growths in different parts of the body. Polyps can also occur in the upper gastrointestinal tract, especially in the duodenum, which is the upper part of the small intestine^[1]. Gastric fundic gland polyps may develop in the stomach^[4].

Some individuals develop benign growths in their bones called osteomas, cysts in their skin, or masses on their adrenal glands^[1][4]. Fibrous tumors called desmoid tumors develop in 10 to 30 percent of people with FAP, usually in the abdomen or abdominal wall^[1][4]. Dental abnormalities may occur, including teeth that do not break through the gums, missing teeth, or extra teeth^[5].

Many people with FAP have an eye condition called congenital hypertrophy of the retinal pigment epithelium (CHRPE). This appears as flat spots on the retina at the back of the eye, which can be seen during an eye exam but does not cause vision problems^[5]. This occurs in up to 80 percent of people with FAP^[1].

Risk of Cancer

Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100 percent^[2]. The polyps are nearly certain to develop into colon or rectal cancer, typically by the time a person is in their 40s^[1].

In classic FAP, cancer develops relatively earlier and faster than in people without the condition. Most people with classic FAP will develop colorectal cancer around age 40, and at least 90 percent will develop it by age 50 if they do not have surgery to remove the colon beforehand^[5]. In some cases, cancer can develop even earlier—about 7 percent of affected patients will develop cancer before age 21^[4].

People with the attenuated form have a 70 percent lifetime risk of colorectal cancer, with cancer typically developing around age 55^[5].

Besides colorectal cancer, people with familial adenomatous polyposis also have an increased risk of developing other cancers. These include duodenal cancer (affecting about 8 percent of people), papillary thyroid cancer (2 percent), pancreatic cancer (2 percent), hepatoblastoma, a type of liver cancer (1.5 percent), and stomach cancer (1 percent)^[2]. Brain and spinal tumors occur in less than 1 percent of cases^[2].

How the Condition Is Diagnosed

If you are at risk of familial adenomatous polyposis because of family history, it is important to be screened frequently, starting in childhood^[7]. Children in families known to be affected by the condition should begin yearly colonoscopy screenings at age 10^[2]. The American College of Gastroenterology recommends annual sigmoidoscopy beginning at ages 10 to 12 years for people with a genetic diagnosis of FAP or family members at risk who have not had genetic testing^[7].

A sigmoidoscopy is a procedure in which a flexible tube is inserted into the rectum to inspect the rectum and the last part of the colon. Once polyps are found in the colon, a colonoscopy is recommended. During a colonoscopy, a tube is inserted into the anus to view the inside of the entire colon^[7].

An esophagogastroduodenoscopy (EGD) uses scopes to inspect the esophagus, stomach, and upper part of the small intestine (duodenum). Both front-view and side-view scopes may be used to examine different areas, including the ampulla of Vater in the duodenum^[7].

Imaging tests of the abdomen and pelvis, such as CT or MRI scans, may be used to evaluate desmoid tumors^[7].

A simple blood test can determine if you carry the abnormal gene that causes FAP through genetic testing^[7]. Your doctor may suggest genetic testing if you have family members with FAP or if you have some, but not all, signs of FAP. Genetic testing can identify whether you are at risk of complications even before polyps develop. This allows children who carry the gene to start appropriate screening and treatment early, which greatly reduces the risk of cancer^[7].

Treatment and Management

To manage the risk of cancer, healthcare providers usually recommend complete removal of the colon, called a total colectomy, and sometimes the rectum too, called a proctocolectomy^[2]. Most people with familial adenomatous polyposis will need surgery to remove the large intestine to prevent cancer^[1]. Because polyps in FAP appear too frequently to manage them one by one, surgery offers substantial risk reduction for colorectal cancer development^[4].

Colectomy is typically recommended during the late teenage years to early twenties, once polyps are detected but before cancer develops^[4]. However, if polyps have advanced features that suggest a higher cancer risk, surgery may be recommended earlier. After the colon is removed, surgeons usually create a neoreservoir, often called an ileoanal pouch, to allow waste to pass from the body^[4].

Some medications have been used to reduce the number and size of polyps. Drugs such as celecoxib and sulindac have been used successfully for this purpose^[1]. However, these drugs are not sufficient as a primary treatment and cannot replace surgery^[12].

Polyps in the duodenum can develop cancer but can usually be managed by careful monitoring and by removing polyps regularly^[1]. Some patients who are at high risk may benefit from screening with endoscopic ultrasound for tumors in and around the ampulla^[12].

Ongoing Monitoring

Even after colon removal surgery, people with familial adenomatous polyposis need to continue regular screenings for other tumors, and possibly additional surgeries to manage those tumors^[2]. Screening for upper gastrointestinal and extraintestinal disease is crucial in managing affected individuals^[4].

After surgery, sigmoidoscopic surveillance and removal of any polyps in the retained rectum or ileal pouch should be performed every 3 to 6 months^[12]. There is an increased risk for polyps and cancer in the ileal pouch, so continued monitoring is essential^[12].

Front- and side-view esophagogastroduodenoscopy should be performed every 1 to 3 years once the diagnosis is made and after surgical therapy^[12]. This allows for detection of gastric and duodenal polyps and examination of the ampulla of Vater.

Because people with FAP face an elevated risk of other cancers such as gastric and duodenal adenocarcinoma, hepatoblastoma, and desmoid tumors, timely screening for associated cancers enables early detection and intervention^[4].