What is APC-associated adenomatous polyposis?
APC-associated adenomatous polyposis includes three diseases caused by mutations – or genetic changes – in the APC gene, namely familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), and stomach cancer with proximal polyposis (gastric adenocarcinoma and proximal polyposis of the stomach, GAPPS).
Starting in adolescence, FAP usually leads to the development of hundreds to thousands of polyps (protrusions of mucous membrane) that are located in the gastrointestinal tract, most frequently in the large intestine. These polyps can progress and result in malignant diseases, such as colon cancer. In addition, there is an increased risk that other benign and malignant tumors will develop.
AFAP is a variant of FAP which is characterized by fewer polyps and a later onset of malignant disease.
GAPPS is characterized by a large number of gastric polyps and an increased risk of stomach cancer. It rarely affects the intestine.
How is APC-associated adenomatous polyposis diagnosed?
Clinical Diagnostics
APC-associated adenomatous polyposis is suspected in a person who exhibits at least one of the following:
In addition, genetic testing for an APC mutation should be considered with presentation of the following: early onset of colon cancer with few or no polyps, dental abnormalities (e.g. excess teeth), odontomas (benign tumors of the tooth-forming tissue), osteomas (benign bone tumors), epidermoid cysts (benign cysts arising from skin cells), benign or malignant tumors of the duodenum, multiple polyps in the stomach, or cancer of the stomach, pancreas, or small intestine.
Genetic Diagnostics
The diagnosis of “APC-associated adenomatous polyposis” is confirmed by the detection of a mutation – or genetic change – in the APC gene.
Diagnostic Criteria
The diagnosis of familial adenomatous polyposis (FAP) is confirmed by detection of a mutation in the APC gene and presentation of one of the following:
The diagnosis of attenuated familial adenomatous polyposis (AFAP) is confirmed by the detection of a mutation in the APC gene and:
The diagnosis of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is confirmed in patients presenting with the following:
What is the risk of cancer?
Familial Adenomatous Polyposis
With FAP, the first polyps usually do not occur until late childhood or adolescence. Over the course of years, the number of polyps constantly increases, with around 95% of FAP patients developing polyps by the age of 35. These polyps have a tendency to progress and invariably lead to the development of colon cancer if left untreated. While the average age here is 39 years, 7% of untreated FAP patients have already developed colon cancer by the age of 21.
In addition to colon cancer, the risk of developing other malignant diseases is also higher. Around 40% of FAP patients with colon cancer develop another malignant tumor.
Disease | Risk of Disease |
---|---|
Cancer of the small intestine | 4-12% |
Pancreatic cancer | Approx. 1% |
Papillary thyroid cancer | 1-12% |
Medulloblastoma | <1% |
Hepatoblastoma | 1,6% |
Biliary tract cancer | minor, but increased |
Stomach cancer | <1% |
Benign changes occur as part of FAP as well:
Manifestation | Frequency of Occurrence with FAP |
---|---|
Osteomas (benign bone tumors) | 20% |
Dental abnormalities, benign tumors of the tooth-forming tissue | 17% |
Congenital hypertrophy of the retinal pigment epithelium (CHRPE) | 75% |
Benign skin lesions (e.g. epidermoid cysts, fibromas) | Unknown |
Desmoid tumors (in part provoked by surgical interventions) | 10-30% |
Space-occupying lesions in the area of the adrenal glands | 7-13% |
Attenuated Familial Adenomatous Polyposis
With AFAP, way fewer polyps occur than with FAP (30 polyps on average). While there is also an increased risk of colon cancer with AFAP, the average age at diagnosis is 50-55 and therefore much higher than with FAP.
In addition to colon cancer, AFAP also involves an increased risk of other gastrointestinal polyps/cancer and thyroid cancer. Diseases outside of the gastrointestinal tract occur as with FAP, although CHRPE and desmoid cysts are rarer.
Stomach Cancer with Proximal Polyposis
In this clinical picture, which was first described in 2012, numerous polyps that can lead to stomach cancer develop in the stomach fundus. The risk of stomach cancer is greater compared to FAP and AFAP, but there is no increased risk that colon cancer will develop.
What causes APC-associated adenomatous polyposis?
APC-associated adenomatous polyposis is caused by a mutation – or genetic change – in the APC gene. This gene encodes for the APC protein, which is responsible for breaking down another protein, β-catenin. β-catenin in turn regulates cell division and by extension cell proliferation.
Now if the APC gene is present in an altered form, β-catenin will no longer be broken down by the APC protein. The resulting massive amount of β-catenin therefore results in the unregulated proliferation of cells, which leads to the formation of polyps and tumors.
Most of the people affected inherited the genetic change from a parent. Around 75-80% of patients have a parent who also suffers from APC-associated adenomatous polyposis. It is inherited as an autosomal dominant disorder.
Is there a treatment?
The treatment of colon cancers or their preliminary stages mainly involves the surgical removal of the colon (colectomy). This is recommended for FAP as soon as adenomas (benign tumors that are regarded as a preliminary stage of cancer) occur; however, the procedure may be delayed depending on the size, histology, and number of adenomatous polyps present. If colon cancer is diagnosed, a colectomy is inevitable.
A colectomy is frequently necessary for AFAP as well. But approximately one third of cases only require removal the polyps by colonoscopy.
No general recommendations are available for GAPPS to date.
Surveillance Recommendations for the Early Detection of Cancer
Surveillance Recommendations
FAP
Colon Cancer and other Cancers of the GastrointestinalTract
Thyroid Cancer
Hepatoblastoma
Desmoid Tumors
Medulloblastoma
AFAP
Colon cancer and other cancers of the gastrointestinal tract
Thyroid Cancer
Medulloblastoma
GAPPS
It is as yet unknown whether surveillance examinations for the early detection of stomach cancer or precautionary removal of the stomach yield positive results.
Self-Care and Support
What should I pay special attention to?
You should see a doctor as soon as you develop symptoms affecting the gastrointestinal tract. They may involve blood or mucous in the stool, stool abnormalities such as diarrhea or constipation, flatulence, or pain. Even non-specific signs such as weight loss should be paid attention to and reported to a doctor so that he or she can check whether you have colon cancer.
You should also see a doctor right away if you notice any other newly occurring anomalies or symptoms, such as difficulty swallowing, skin lesions, abdominal pain, headaches, or dizziness.