Familial adenomatous polyposis (FAP) is an inherited syndrome of a very high risk of colorectal cancer (bowel cancer). Inherited or hereditary syndromes are health conditions that are passed from parents to children. FAP makes up fewer than 1% of CRC cases. There are three subtypes: classic FAP, attenuated FAP, and MYH-associated (also called MUTYH-associated polyposis or autosomal recessive FAP).
Classic and attenuated FAP are characterized by hundreds to thousands of colorectal adenomatous polyps (adenomas) which are abnormal growths in the colon and rectum that are precancerous. If they are not removed and are left untreated, they will become malignant. The APC gene is involved in maintaining normal cell growth. When a mutation disrupts that function, abnormal growth occurs leading to these colon polyps and rectal polyps.
The timeline of polyp growth and cancer development is different in classic FAP and attenuated FAP. The average age of colorectal cancer is 39 years in patients with classic FAP. For attenuated FAP, the average age of colon cancer or rectal cancer development is 55.
MYH-associated polyposis is characterized by fewer adenomatous polyps than classic FAP or attenuated FAP, usually fewer than 100. MYH (also known as MUTYH) is a gene involved with repairing DNA damage in cells. When MYH is mutated, cells are unable to repair DNA damage and mutations build up in genes that lead to abnormal cell growth and polyps. Most MYH-associated colorectal cancer occurs between 40 and 60 years of age.
Genetic testing is performed on a blood sample or on cells collected from your mouth or saliva. Testing for FAP is often accompanied by consultation with a genetic counselor, a healthcare provider with cancer genetics training. Genetic counselors provide risk assessment, education, and support for patients and families that may be affected by a genetic syndrome.
If you have FAP, your report will say “positive”, “pathogenic mutation detected”, or “variant detected, likely pathogenic” and will give the gene location of the specific mutation found and in which gene, APC or MYH. If you do not have FAP, your results will be reported as “wild-type”, “negative” or “no pathogenic mutation detected”.
If you have no APC or MYH mutation (wild-type)
If you do have a pathogenic APC gene mutation or MYH gene mutation
In addition to large intestine (colorectal) tumors, patients with all three types of FAP (classic FAP, attenuated FAP, and MYH-associated polyposis) are at increased risk for other gastrointestinal tract cancers, including cancer of the stomach (gastric) and small intestine (small bowel), especially the duodenum. FAP is also associated with higher risk of cancer of the pancreas, liver (hepatic) and bile duct cancer, adrenal gland tumors, thyroid cancer, and some central nervous system tumors, especially brain medulloblastoma. These risks vary by the location of the mutation in the APC gene. If you have familial adenomatous polyposis, talk to your oncology team about screening and prevention of other FAP associated cancers.
In addition to malignant conditions, FAP is associated with several kinds of benign tumors including osteomas (benign bone tumors) and desmoid tumors (benign connective tissue tumors), congenital tooth (dental) abnormalities, and an asymptomatic eye abnormality called congenital hypertrophy of the retinal pigment epithelium (CHRPE).
Before it was discovered that these varied conditions were related by APC gene mutation, and all part of the Familial Adenomatous Polyposis spectrum of disease, there were other names for the combinations of these conditions. Turcot Syndrome referred to FAP patients with colorectal polyps and an associated primary brain tumor. Gardner Syndrome referred to FAP patients with colorectal polyps, other FAP associated cancers, osteomas, dental abnormalities, and skin abnormalities called epidermoid cysts.
Because FAP is inherited, it is critical that your biological family members know about your FAP diagnosis and have their own genetic testing. If you have had genetic counseling as part of your FAP testing process, your genetic counselor can help you with information for your family members. Family members who are tested and subsequently diagnosed with FAP have earlier (starting at age 10) and more frequent (yearly) colorectal cancer screening, removal of precancerous polyps through colonoscopy, and may have a preventive (prophylactic) colectomy. Family members with FAP will also need screening and preventive care for other FAP associated cancers.
All colorectal cancer patients with more than 20 cumulative adenomatous polyps (precancerous growths in the colon and rectum) should be tested for FAP. All biological family members (parents, siblings, children, cousins) of CRC patients with FAP should also be tested. An early FAP diagnosis can prevent colorectal cancer in family members.
Juvenile polyposis syndrome (JPS) is a related colorectal polyp syndrome with a lifetime risk of colorectal cancer of 34-38%. It is characterized by fewer polyps than FAP (5-100) and is caused by different gene mutations. 60% of JPS is caused by currently unknown mutations, 20% by BMPR1A mutation, and 20% by SMAD4 mutation. BMPR1A and SMAD4 are genes involved in tumor suppression. Mutations in these genes allow abnormal growth, leading to polyps. The colorectal polyps in JPS are benign hamartomatous polyps. But, like FAP polyps, if they are not removed, they may become cancer. Colorectal cancer associated with JPS is treated with surgery, and additional treatments (chemotherapy, targeted therapy, immunotherapy) may be used based on cancer stage, tumor biomarkers, and other patient factors. JPS is inherited and biological family members need to know about your JPS diagnosis and have their own cancer screening and genetic testing. Like FAP, JPS is associated with several digestive system cancers, so talk to your oncology team about screening and prevention of JPS associated cancers.
A biomarker is a piece of information about your health. Biomarkers include your blood pressure, your blood type, and cholesterol or blood sugar levels measured in a blood test. The biomarkers of cancer are also known as tumor markers.
