What is FAP syndrome?
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the colon and rectum. People with the classic type of FAP may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years (screening usually begins at 8 to 10 years old). The type of polyp most often seen in FAP syndrome, called an adenoma, is precancerous and has the potential to develop into cancer. Unless the growths are removed, these polyps may become malignant (cancerous). The average age at which an individual develops colorectal cancer in classic FAP is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis (AFAP), which develops fewer polyps. The average age of colon cancer onset for those with AFAP is 55 years.
In people with classic FAP, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic FAP and AFAP, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.
Approximately 2% of all colon cancer is thought to be caused by a hereditary adenomatous polyposis condition. They can be categorized into three conditions:
Familial adenomatous polyposis (FAP)
Attenuated familial adenomatous polyposis (AFAP)
MYH-associated polyposis (MAP)
Classic familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene. Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as “biallelic MYH mutations”). Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected).
When assessing hereditary cancer risk, a patient’s personal and family history is collected to investigate the risk for a polyposis syndrome. Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient. It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC mutation may be present in an individual even if it is absent in both parents.
Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with polyps or cancer. Genetic testing is the only way to identify truly at-risk family members.
Finding patients at risk for adenomatous polyposis syndromes and following up with them is perhaps the most critical step in changing hereditary cancer outcomes.