APC Gene Mutations
Familial Adenomatous Polyposis syndrome (FAP) or Attenuated Familial Adenomatous Polyposis syndrome (AFAP)
What does it mean to have an APC gene mutation and a diagnosis of Familial Adenomatous Polyposis (FAP) or Attenuated FAP (AFAP) syndrome?
People with mutations in the APC gene have a high risk for developing large numbers of pre-cancerous polyps in their colon and rectum. Each of these polyps can develop into a cancer, and since there are so many of them, the risk for colorectal cancer is very high. Individuals with APC mutations who develop more than 100 polyps are said to have Familial Adenomatous Polyposis syndrome (FAP). People who have fewer than 100 polyps due to their APC gene mutation are said to have a milder form of the condition, which is called Attenuated FAP syndrome (AFAP). People with AFAP have a lower risk for colorectal cancer than people with FAP, but the risk is still very high.
Other symptoms of FAP and AFAP include a higher than average risk for gastric (stomach), small bowel, thyroid, brain and possibly pancreatic cancer. During childhood, there is an increased risk for hepatoblastoma, a kind of liver cancer. Some people have non-cancerous symptoms, such as desmoid tumors (a non-cancerous growth of connective tissue), dental abnormalities, growths on bones, skin cysts and an eye abnormality called congenital hypertrophy of the retinal pigment epithelium (CHRPE). All of these things are more likely to occur in people with FAP compared to people who have AFAP.
What can be done to protect individuals with an APC mutation?
The National Comprehensive Cancer Network (NCCN) provides detailed recommendations for lowering the risk of cancer in people with mutations in the APC gene. Because of the high risk for colorectal cancer, people with APC mutations should begin screening with colonoscopies at young ages (10-15 years) and have them done every year. As people get older, complete removal of the colon may be recommended. This may be the best choice if there are too many polyps to remove with regular colonoscopies or if it is believed that this is the most reliable way to prevent colorectal cancer.
There are also recommendations for screening to reduce the risk of the other cancers that can occur in people with FAP or AFAP. These recommendations are complicated, so it is recommended that people with FAP or AFAP be cared for by healthcare professionals with experience treating this condition.
Associated Syndrome Name: Familial Adenomatous Polyposis (FAP)/Attenuated Familial Adenomatous Polyposis (AFAP)
APC Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
APC gene Overview
- Individuals with APC mutations have either Familial Adenomatous Polyposis syndrome (FAP) or Attenuated Familial Adenomatous Polyposis syndrome (AFAP). The distinction between FAP and AFAP is based on the number of adenomatous polyps found in the patient, as described below.
- Patients with FAP/AFAP have a greatly increased risk for colorectal cancer, often at very young ages.
- Patients with FAP/AFAP are likely to develop large numbers of adenomatous polyps in the GI system, particularly in the colon, rectum, stomach and small bowel. Patients with 100 or more polyps are said to have a diagnosis of FAP and patients with less than 100 polyps are said to have a diagnosis of AFAP. These polyps begin to form at an average age of 16, but can be found in individuals as young as age 7.
- Patients with FAP/AFAP also have a high risk for other cancers, most notably small bowel and periampullary cancer. There are also elevated risks for childhood hepatoblastoma, and cancers of the thyroid, pancreas, and central nervous system (CNS).
- Gastric polyps are common, but the risk for gastric cancer is not thought to be significantly increased in patients living in Western cultures. A more significantly increased risk for gastric cancer has been observed in Japanese and Korean patients.
- Patients with FAP, and less commonly, patients with AFAP, can have clinical findings other than cancer, such as osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE) and benign cutaneous lesions. Desmoid tumors, which occur in some individuals with FAP, are the most serious cause of morbidity among affected individuals outside of cancer, and may be triggered by abdominal surgery.
- Although there are high risks for cancer in patients with FAP/AFAP, these risks can be greatly reduced with appropriate medical management. Guidelines from the National Comprehensive Cancer Network (NCCN) are listed below. It is recommended that patients with APC mutations and a diagnosis of FAP or AFAP be managed by a multidisciplinary team with experience in the prevention and treatment of the complications associated with hereditary colorectal cancer conditions.
APC gene Cancer Risk Table
|Cancer Type||Age Range||Cancer Risk||Risk for General Population 3|
|Colorectal||FAP to age 211, 2||7%||<0.1%|
|FAP to age 501, 2||93%||0.3%|
|FAP to age 801, 2||>99%||3.0%|
|AFAP to age 801, 2||>70%||3.0%|
|Other - Desmoid Tumors||To age 801||10%-30%||<0.04%|
|Small Bowel/Periampullary||To age 801, 2||4%-12%||0.2%|
|Hepatoblastoma||To age 51, 2||1%-2%||<0.001%|
|Gastric||To age 801, 2, 4||Slightly increased risk in Western cultures, but may be significantly increased in cultures with a higher baseline gastric cancer rate.||0.6%|
|Thyroid||To age 801, 2||1%-2%||1.1%|
|Central Nervous System||To age 801, 2||1%||0.5%|
|Pancreatic||To age 801, 2||Possibly elevated risk||1%|
APC Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.
This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.
|Cancer Type||Procedure||Age to Begin||Frequency|
|Colorectal||Sigmoidoscopy or colonoscopy2||10 to 15 years||Annually|
|Colorectal surgical evaluation and counseling.2, 5, 6||Based on cancer diagnosis and/or polyp number, size and histology||NA|
|Consider chemoprevention with NSAIDs to reduce adenoma burden after surgery.2||NA||NA|
|Other - Desmoid Tumors||Abdominal palpation with consideration of abdominal MRI or CT.2||1 to 3 years post-colectomy||Every 5 to 10 years, or with symptoms|
|Small Bowel/Periampullary||Upper endoscopy, including complete visualization of the ampulla of Vater2||20 to 25 years, or earlier if patient had a colectomy before age 20 years||Every 4 years|
|Hepatoblastoma||Consider liver palpation, abdominal ultrasound, and alpha-fetoprotein (AFP) measurement.2||Infancy||Every 3 to 6 months during first 5 years of life|
|Gastric||Upper endoscopy2, 4||20 to 25 years, or earlier if patient had a colectomy before age 20 years||Every 4 years|
|Thyroid||Thyroid examination and/or consider ultrasound.2||Late teens||Annually|
|Central Nervous System||Physical examination2||Individualized||Annually|
|Pancreatic||Currently there are no specific medical management guidelines for pancreatic cancer risk in mutation carriers.||NA||NA|
Information for Family Members
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the APC gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.
Since APC mutations carry a risk for complications in children and some screenings are recommended to begin at young ages, consideration should be given to the possibility of mutation testing in childhood.7
Approximately 20% of individuals with FAP/AFAP have not inherited the APC mutation from a parent. In these cases the mutation has developed spontaneously in that individual (a de novo mutation). Once this occurs, the children of that individual are each at 50% risk of inheriting the mutation.
- Jasperson KW, et al. APC-Associated Polyposis Conditions. 2017 Feb 2. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1345/ PMID: 20301519.
- Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2017. October 10. Available at http://www.nccn.org.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2017. August 22. Available at http://www.nccn.org.
- Achatz MI, et al. Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. Clin Cancer Res. 2017 23:e107-e114. PMID: 28674119.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
- Aretz S, et al. Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP). Hum Mutat. 2007 28:985-92. PMID: 17486639.