"APC-Associated Adenomatous Polyposis" – What is It?
APC-associated adenomatous polyposis comprises three diseases based on mutations, or genetic changes, in the APC gene. These are familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP) and gastric carcinoma with proximal polyposis (gastric adenocarcinoma and proximal polyposis of the stomach, GAPPS).
In FAP, hundreds to thousands of polyps (mucosal protrusions) usually appear in adolescence and are localised in the gastrointestinal tract, most commonly in the colon. These polyps can degenerate and lead to malignant diseases such as bowel cancer. There is also an increased risk of developing other benign and malignant tumours.
AFAP is a variant of FAP with significantly fewer polyps and a later onset of cancer.
GAPPS is characterised by a large number of polyps in the stomach and an increased risk of stomach cancer. The bowel is rarely affected.
How Is "APC-Associated Adenomatous Polyposis" Diagnosed?
Clinical Diagnostics
APC-associated adenomatous polyposis is suspected in a person who has at least one of the following findings
- Multiple polyps in the large bowel (at least 10-20)
- Relatives with multiple polyps in the colon and/or non-gastrointestinal manifestations
- Congenital hypertrophy of the retinal pigment epithelium, CHRPE (retinal pigment patches)
- Desmoid tumour (connective tissue tumour that often occurs after surgery)
- Papillary thyroid cancer
- Certain form of medulloblastoma (malignant brain tumour) (known as WNT-activated, CTNNB1 wild-type)
- A certain type of hepatoblastoma (malignant tumour of the liver), known as hepatoblastoma without CTNNB1 mutation.
In addition, genetic testing for APC mutation should be considered in the following findings Early-onset colorectal cancer with few or no polyps, dental abnormalities (e.g., supernumerary teeth), odontomas (benign tumours of tooth-forming tissue), osteomas (benign bone tumours), epidermoid cysts (benign cysts formed from skin cells), benign or malignant tumours of the duodenum, multiple polyps in the stomach, gastric, pancreatic, or small bowel cancer.
Genetic Diagnostics
The diagnosis of APC-associated adenomatous polyposis is confirmed by the detection of a mutation, i.e. a genetic change, in the APC gene.
Diagnostic Criteria
The diagnosis of Familial Adenomatous Polyposis (FAP) is confirmed by genetic evidence of a mutation in the APC gene and one of the following findings
- At least 100 polyps in the colon (in young patients or after removal of the colon, there may be fewer than 100 polyps)
- Several, but fewer than 100 polyps and one relative with confirmed FAP
The diagnosis of Attenuated Familial Adenomatous Polyposis (AFAP) is confirmed by genetic evidence of a mutation in the APC gene:
- One or more relatives with confirmed AFAP and/or
- Fewer than 100 polyps in the colon or
- More than 100 polyps in the bowel at an advanced age (>40 years)
The diagnosis of Gastric Carcinoma with Proximal Polyposis (GAPPS) is confirmed in patients with the following findings
- Gastric polyps confined to the corpus and fundus (body and base of the stomach)
- More than 100 polyps in the upper stomach (corpus and fundus), or more than 30 polyps in a first-degree relative
- Predominantly polyps in the gastric fundus; some have areas of altered tissue structure (or a relative with altered polyps in the gastric fundus or with gastric cancer)
- Autosomal dominant pattern of inheritance
- No evidence of polyps in the colon or duodenum
What Is the Risk of Cancer?
Familial Adenomatous Polyposis
In FAP, the first polyps usually appear in late childhood or adolescence. The number of polyps increases steadily over the years to hundreds or thousands, so that by the age of 35, around 95% of people with FAP have polyps. These polyps have a tendency to degenerate, which almost always leads to bowel cancer if left untreated. The average age is 39, but 7% of untreated FAP patients develop bowel cancer by the age of 21.
In addition to bowel cancer, there is an increased risk of developing other malignancies. About 40% of FAP patients with colorectal cancer develop another malignancy.
| Disease | Risk of disease |
|---|---|
| Small bowel cancer | 4-12% |
| Pancreatic carcinoma | approx. 1% |
| Papillary thyroid carcinoma | 1-12% |
| Medulloblastoma | <1% |
| Hepatoblastoma | 1.6% |
| Biliary duct carcinoma | low, but increased |
| Gastric carcinoma | <1% |
Benign changes also occur in the context of FAP:
| Manifestation | FAP incidence |
|---|---|
| Osteomas (benign bone tumors) | 20% |
| Tooth abnormalities, benign tumors of the tooth-forming tissue | 17% |
| Congenital hypertrophy of the retinal pigment epithelium (CHRPE) | 75% |
| Genetic skin lesions (e.g. epidermoid cysts) | |
| .e.g. epidermoid cysts, fibromas) | unknown |
| Desmoid tumors (in part provoked by surgical interventions) | 10-30% |
| Space requirements in the area of the adrenal glands | 7-13% |
Attenuated Familial Adenomatous Polyposis
There are significantly fewer polyps in AFAP than in FAP (30 polyps on average). There is also an increased risk of colorectal cancer in AFAP, although the average age at diagnosis is 50-55 years, which is higher than in FAP.
In addition to colorectal cancer, AFAP is associated with an increased risk of other gastrointestinal polyps and cancers, as well as thyroid cancer. Non-gastrointestinal disease occurs as in FAP, but CHRPE and desmoid cysts are less common.
Gastric Carcinoma with Proximal Polyposis
This condition, first described in 2012, involves numerous polyps in the lining of the stomach that can lead to stomach cancer. The risk of developing stomach cancer is increased compared to FAP and AFAP, but there is no increased risk of developing colorectal cancer.
What Is Known About the Development of APC-Associated Adenomatous Polyposis?
APC-associated adenomatous polyposis is caused by a mutation, or genetic change, in the APC gene. This gene codes for the APC protein, which ensures that another protein, β-catenin, is degraded. Beta-catenin, in turn, ensures that cells divide and thus multiply.
If the APC gene is present in an altered form, β-catenin is no longer degraded by the APC protein. As a result, the abundant β-catenin ensures uncontrolled cell proliferation, leading to the formation of polyps and tumours.
The genetic mutation is usually inherited from one parent. About 75-80% of patients have a parent with APC-associated adenomatous polyposis. The inheritance pattern is autosomal dominant.
Is There Any Form of Treatment Available?
The main treatment for colorectal cancer or its precursors is surgical removal of the colon (colectomy). This is recommended for FAP as soon as adenomas (benign tumours considered to be precancerous) appear, but may be delayed depending on the size, histology and number of adenomatous polyps. If bowel cancer is diagnosed, colectomy is inevitable.
In AFAP, colectomy is also often necessary. However, in about a third of cases, it is enough to remove the polyps with a colonoscopy.
There are no standardised recommendations for GAPPS yet.
Diagnosis of APC-Associated Adenomatous Polyposis- What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some useful tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnose APC-Associated Adenomatous Polyposis. Wie geht es weiter?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some useful tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
The aim is to detect developing complications early to achieve the best treatment results. To this end, the AACR guidelines 2024 recommend regular medical check-ups:
FAP
Colon Cancer and Other Carcinomas of the Gastrointestinal Tract
- Colonoscopy from 10-15 years; annually until surgery
- Gastroscopy from 20-30 years of age (recommendations vary); every 6 months to every 4 years (depending on the number, size, histology and tissue changes of the polyps)
Thyroid Carcinoma
- Initiate thyroid cancer screening with ultrasound for all patients with Familial Adenomatous Polyposis (FAP) starting at age 16 and repeating ultrasound screenings every 2 years
- Physical exams are not preferred for screening papillary thyroid carcinoma (PTC) due to their lower sensitivity
- Consult with a pediatric endocrinologist experienced in evaluating thyroid nodules and tumor predisposition syndromes
Hepatoblastoma
- Patients with familial adenomatous polyposis (FAP) should undergo screening for hepatoblastoma
- The recommended screening for FAP patients includes abdominal ultrasounds and serum AFP testing every 3 months, starting from the time of FAP diagnosis until they reach 7 years of age
Desmoid Tumors
- Abdominal examination; yearly
- MRI/CT abdomen and pelvis for family history of desmoid tumours; within the first three years after colectomy, then every 5-10 years
Medulloblastoma
- Clinical neurological examination from childhood; annually
- Annual neurologic examinations should be conducted carefully. Parents should be educated about the signs and symptoms of brain tumors, such as severe or worsening headaches, headaches accompanied by vomiting, and focal neurologic symptoms. A low threshold for rapid evaluation with neuroimaging is essential.
AFAP
Colon Cancer and Other Carcinomas of the Gastrointestinal Tract
- Colonoscopy from age 15-19; every 3 years until adenomas appear, then annually
- Gastroscopy from age 20-30 (recommendations vary); every 6 months to every 4 years (depending on number, size, histology and tissue changes of polyps)
Thyroid Carcinoma
- Palpatory examination, possibly ultrasound of the thyroid gland from 15-19 years; annually
Medulloblastoma
- Clinical neurological examination from childhood; annually
GAPPS
Screening with upper endoscopy is recommended to begin at age 15. Prophylactic gastrectomy should be considered between the ages of 30 and 35, especially if there are fundic gland polyps, dysplasia, or a family history of cancer. It is important to note that GAPPS does not indicate a high risk for colorectal cancer; however, a baseline colonoscopy should be performed once at age 15.
APC-Associated Adenomatous Polyposis – What You Can Do Yourself
You Should Pay Attention to the Following
You should consult a doctor as soon as you experience gastrointestinal tract symptoms. These can include blood or mucus discharge from the bowel, stool abnormalities such as diarrhea or constipation, flatulence, or pain. However, non-specific signs such as weight loss should also be noticed and reported to a doctor so that colon cancer can be investigated.
You should also urgently consult a doctor if you notice any other new abnormalities or complaints, such as difficulty swallowing, skin lesions, abdominal pain, headaches, or dizziness.
Further Information
Patients can also register for the KPS register at any time or have this done by the doctors looking after them.
Any further questions?
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