Hereditary Colorectal Cancer Syndromes: Familial Adenomatous Polyposis (FAP)

Hereditary Colorectal Cancer Syndromes: Familial Adenomatous Polyposis (FAP)

March 21, 2017

Hereditary Colorectal Cancer Syndromes: Familial Adenomatous Polyposis (FAP) 

Familial adenomatous polyposis (FAP), also known as familial polyposis coli, adenomatous polyposis coli, or Gardner syndrome, accounts for about 1% of colorectal cancers in the United States. The incidence varies from 1 in 7,000 to 1 in 22,000 live births. It affects males and females equally. The term Gardner syndrome has sometimes been used to refer to patients who also have tumors outside the colon, such as osteomas (benign bony growths) and soft tissue tumors.

In its classic form, FAP is characterized by the following:

  • Polyposis. The development of multiple (more than 100) benign (noncancerous) adenomatous polyps in the colon and rectum. These are described as having a dense carpet-like appearance on colonoscopy or sigmoidoscopy. Although these polyps are benign, they can turn cancerous.

  • Early age of onset. Polyps begin to develop at an average age of 16 years (range of 7 to 36 years).

  • A nearly 100% risk of colorectal cancer in the absence of treatment for polyposis (colectomy, or surgery to remove the colon)

  • An autosomal dominant pattern of inheritance (inherited from a mother or father with the disorder)

  • An increased risk of other health problems, such as polyps in the upper gastrointestinal tract, osteomas, epidermoid cysts (skin lesions). Also, desmoid tumors (locally invasive tumors that grow aggressively and can be life-threatening), congenital hypertrophy of retinal pigment (CHRPE), and dental abnormalities

  • An increased risk of thyroid, small bowel, pancreatic, and stomach cancers, brain tumors, and hepatoblastoma (a childhood liver tumor)

Mutations in a gene called APC causes most cases of FAP. The APC gene is a tumor suppressor gene. It usually has the job of controlling cell growth and cell death. Everyone has two APC genes (one on each chromosome #5). When a person has an altered, or mutated, APC gene, his or her risk of developing polyps and risk of cancer increases. 

Almost all people who have a mutation in the APC gene that causes the classic form of FAP will develop colorectal polyps by their 40s or 50s if nothing is done about it. However, when it starts isn't the same for everyone. Consider the following:

Age of onset

People who have a mutant APC gene who will have adenomas in the colon

10 years


20 years


30 years


Because FAP starts at an early age, cancer screening often begins in childhood. In addition, genetic testing of children at risk is a special consideration. Usually, genetic tests are not a choice for people who are considered minors unless there is some type of medical benefit available to justify testing. FAP is an autosomal dominant cancer genetic syndrome. This means that a child whose parent has the condition has a 50/50 chance of inheriting the familial APC gene mutation. There is equally as likely a chance the child will not inherit the familial APC mutation. This would spare the child from having to undergo annual exams (for example, sigmoidoscopy or colonoscopy) if he or she was found not to have the APC gene mutation. Since genetic testing can affect medical management, genetic testing of children at risk of classic FAP is a choice that can be considered.

Both copies of a tumor suppressor gene must be altered, or mutated, before a person will develop polyps or cancer. In FAP, the first mutation is usually inherited from either the mother or the father. It is therefore present in all cells of the body. This is called a germline mutation. It is not until the second copy of the gene is mutated in, for instance, a colon cell, that a polyp develops. In order for a benign polyp to become malignant (cancerous), the polyp must gain mutations in several additional growth control genes. Loss of both copies of APC is just the first step in the process of cancer development. What causes these additional mutations to be gained is unknown. Possible causes include chemical, physical, or biological environmental exposures or chance errors in cell copying. Since we do not know how to prevent these mutations from happening, the treatment for classic FAP is a colectomy. This is a removal of the colon once polyps develop, but before they become cancerous.

It is important to remember that the APC gene is not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father's side of the family. In about one fourth of cases, the APC mutation is de novo. This means it was not inherited, but happened for the first time in a family in the person with symptoms. People with de novo mutations can still transmit them in the same inheritance pattern (autosomal dominant). This means there is a 50/50 chance for them to pass the mutation to a child (regardless of gender).

What are genotype-phenotype variations?

Hundreds of mutations have been found throughout the APC gene. It has long been recognized that some families with APC mutations have different symptoms than others. Studies comparing symptoms in patients with different and similar APC mutations have been done to see if there are any correlations. A correlation between specific mutations and symptoms is called a genotype-phenotype correlation. Genotype-phenotype correlation studies for the APC gene have shown that the location of a mutation in the gene provides some information about the types of FAP health problems a person will have. For instance, mutations in certain parts of the gene are associated with an increased rate of desmoid tumors, osteomas, and epidermoid cysts. Where in the gene a mutation lies also provides some information about the number of polyps a person will develop. Even though some correlations exist, there is often variability of symptoms between people who have the same mutation. This is because factors other than the APC mutation (environmental factors, other genetic factors) contribute to the development of polyps and cancer.

What is attenuated FAP?

People with attenuated familial adenomatous polyposis (AFAP) develop fewer than 100 adenomatous polyps (average of 30 polyps). The risk of developing colon cancer is still increased, but the average age of diagnosis is older (about 55 years of age) than in the classic form of FAP. Some of the other health problems associated with classic FAP also happen in the attenuated form. However, cases of congenital hypertrophy of the retinal pigment (CHRPE) are rarely seen.

Mutations in three specific areas of the APC gene have been associated with AFAP. The number of polyps developed and the risk of other ways FAP shows up varies depending on which area the mutation is located.

The incidence of AFAP is unknown, but thought to be about the same or less than classic FAP.

What is a I1307K mutation?

One APC mutation in particular, called I1307K, is present in about 6% of the American Ashkenazi Jewish population. This mutation is associated with a 10% to 20% risk of colorectal cancer (slightly more than double the risk of someone else in the general population). However, people with this mutation do not present with the classic carpet of polyps in the colon seen in FAP.


March 21, 2017


Clinical manifestations and diagnosis of familial adenomatous polyposis, UpToDate

Reviewed By:  

Alteri, Rick, MD,MMI board-certified, academically affiliated clinician