Classic familial adenomatous polyposis, called FAP or classic FAP, is a genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps. An adenomatous polyp is an area where normal cells that line the inside of a person’s colon begin to make mucous and form a mass on the inside of the intestinal tract.
The average age for polyps to develop in people with FAP is in the mid-teens. More than 95% of people with FAP will have multiple colon polyps by age 35.
If FAP is not recognized and treated, there is almost a 100% chance that a person will develop colorectal cancer.
There is also an increased chance of developing cancer in the stomach and/or small intestines.
Other types of cancer found in families with FAP include hepatoblastoma, a type of liver cancer seen in young children; desmoid tumors/desmoid fibromatosis, a locally aggressive tumor that does not metastasize; papillary thyroid cancer; pancreatic, adrenal, and bile duct cancers; and a low risk of a type of brain cancer called medulloblastoma.
What are the symptoms of FAP?
Many FAP sufferers are diagnosed because they have an affected relative. This is clearly ideal.
New cases may have the common symptoms of colonic polyps or even colonic cancer if it has already developed.
- rectal bleeding
- iron deficiency anaemia
- abdominal pain
- weight loss.
Rarely patients may come to medical attention for the symptoms from the associated stomach and duodenal polyps or other benign tumours.
Not all symptoms of FAP are cancer-related. Some additional features of FAP may include:
- Osteomas, which are noncancerous bony growths, usually found on the jaw
- Extra, missing, or unerupted teeth
- Congenital, meaning present at birth, hypertrophy of the retinal pigment epithelium (CHRPE). This is an eye condition that does not affect vision, but it is a condition that an eye doctor may see during an examination with a special instrument called an ophthalmoscope.
- Benign (noncancerous) skin changes, such as epidermoid cysts and fibromas
- Adrenal masses
There are three subtypes of classic FAP called attenuated FAP (AFAP), Gardner syndrome, and Turcot syndrome. This section addresses classic FAP.
What causes classic FAP?
FAP is passed from generation to generation in a family. The APC gene is linked to FAP; APC stands for adenomatous polyposis coli. A mutation (alteration) in the APC gene gives a person an increased lifetime risk of developing colorectal cancer or other cancers of the digestive tract.
FAP affects approximately 1 in 10,000 people, men and women equally.
Most cases of FAP are due to a mutation or fault in the adenomatous polyposis coli (APC) gene located on chromosome 5.
Inheritance is autosomal dominant so only one gene (or allele) out of two in each cell is needed to produce the FAP disease.
Usually this is inherited either from the patients mother or father who would also have FAP.
Children of FAP suffers therefore have a 50 per cent chance of inheriting the affected gene.
However in 15 to 20 per cent of cases the disease arises with no relatives affected. The mutation or fault has therefore occurred spontaneously by chance.
It is believed the APC gene is a tumour suppressor gene so if it is abnormal and not working correctly natural growth in the colon is unrestrained and polyps develop.
MAP patients who do not have such severe disease, may have another genetic abnormality on the MUTYH gene.
This gene is recessive, so two defective genes (or alleles) are required to produce the disease, one from each parent.
However the parents will usually be carriers and may not show any signs of colonic polyps.
How is classic FAP inherited?
Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. FAP follows an autosomal dominant inheritance pattern. In autosomal dominant inheritance, a mutation happens in only one copy of the gene.
This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation.
A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.
How common is classic FAP?
FAP is uncommon; specific estimates on how many people have FAP vary from one in 22,000 up to one in 7,000.
About 30% of people with FAP do not have any family history of the condition; they have a de novo (new) mutation in the APC gene.
Most colorectal cancer is sporadic, meaning it occurs by chance, and is not related to FAP or other known inherited genetic changes. Less than 1% of all colorectal cancer is thought to be due to FAP.
How is classic FAP diagnosed?
Classic FAP is a clinical diagnosis. This means that it is typically diagnosed when the doctor finds many polyps, rather than by the results of a laboratory test.
A person with more than 100 adenomatous colon polyps is considered to have FAP. People with FAP can also have a blood test to look for a mutation in the APC gene.
If an APC gene mutation is found, other family members may be diagnosed with FAP if they are tested and have the same gene mutation.
ASCO recommends the following screening for people with FAP. It is important to discuss these options with your doctor, as each individual is different:
- Sigmoidoscopy or colonoscopy every one to two years, starting at age 10 to 11
- Yearly colonoscopy once polyps are found until a colectomy is planned. People with classic
- FAP may need a colectomy, the surgical removal of the entire colon, at some point due to a high number of polyps and the high risk of colorectal cancer.
This is a major surgery and possible side effects may include the need for colostomy. Talk with your doctor about what to expect during and after this surgery.
- Upper endoscopy (EGD) at age 25 to 30 or once colorectal polyps are detected, whichever occurs first
- Yearly ultrasound of the thyroid may be considered starting at age 25 to 30
- Computed tomography (CT) scan or magnetic resonance imaging (MRI) if a person has a family history of desmoid tumors or a mutation on the APC gene that is linked with these tumors
Screening options may change over time as new technologies are developed and more is learned about FAP. It is important to talk with your doctor about appropriate screening tests.
Learn more about what to expect when having common tests, procedures, and scans, and read more about these screening recommendations at www.asco.org/endorsements/HereditaryCRC.
Questions to ask the doctor
If you are concerned about your risk of colorectal cancer or other types of cancer, talk with your doctor. Consider asking the following questions of your doctor:
- What is my risk of developing colorectal cancer?
- How many colon polyps have I had in total?
- What kind of colon polyps have I had? The two most common kinds are hyperplastic and adenomatous.
- What is my risk of developing another type of cancer?
- What can I do to reduce my risk of cancer?
- What are my options for cancer screening?
- If you are concerned about your family history and think your family may have FAP, consider asking the following questions:
- Does my family history increase my risk of colorectal cancer?
- Should I meet with a genetic counselor?
- Should I consider genetic testing?
What else could it be?
Usually a firm diagnosis of FAP is not difficult to make given the number of polyps at a very young age.
Occasionally problems occur when distinguishing older patients with AAPC from individuals with many spontaneous polyps.
What treatment is available?
Children with an affected parent or relatives thought to be at risk should be screened every year from the age of 10 until the age of 35 and every 3 years thereafter.
This is usually by flexible sigmoidoscopy or colonoscopy looking for evidence of colonic polyps.
If FAP is confirmed removal of the colon with all its polyps should be planned to prevent the risk of developing colonic cancer.
Usually surgery is planned by the late teenage years.
The main surgical options for removing the colon in FAP are:
Ileal pouch anal-anastamosis – in this operation the surgeon removes the entire colon and also the rectum or lower part of the colon.
A pouch or reservoir is formed from the far end of the small bowel and joined to the anus directly. This avoids a stoma bag on the abdominal wall and reduces colon cancer risk by removing the entire colon including the rectum.
It has the advantage, particularly in young people, of passing faeces through the normal way. Bowel function is rarely normal afterwards and long term antidiarrhoeal treatment may be required.
Ileo-rectal anastamosis – this operation removes most of the colon but leaves the rectum intact. The small bowel or ileum is directly attached to the upper rectum.
Bowel function is better but there remains a chance of polyps and colon cancer in the rectal remnant. Close repeated inspection of the remaining rectum is required and ultimately the rectum often needs to be removed anyway.
Total colectomy and stoma formation – another option is total removal of the colon and rectum with formation of an ileostomy or stoma on the abdominal wall. Faeces are then passed into a bag on the outer surface of the abdomen.
This is the safest option as all colonic polyps and the entire colon is removed. However a stoma or bag is required which may be difficult for young people to accept.
Duodenal polyps occur in FAP patients but usually at an older age.
Direct visualisation and surveillance for duodenal polyps should start at around 25 to 30 years of age, at least every one to two years
This is done by passing a tube or endoscope through the mouth, usually under sedation.
Polyps in the stomach or duodenum can be removed endoscopically (from the inside) via a tube.
Surgery may be required if polyps are large or have become a cancer.
What is the prognosis in FAP?
Genetic mutation analysis to identify abnormal genes is constantly improving and able to detect most affected individuals.
Patients discovered by screening, before development of serious complications, should do well.
Careful and repeated viewing of the colon and duodenum together with early surgery should improve long term outlook.
Without such treatment colon cancer is inevitable usually before the age of 40 years.
Medical treatment with non-steroidal anti-inflammatory drugs (NSAIDs) to reduce polyp growth has been suggested but is not sufficient to reduce the cancer risk.
Careful endoscopic screening and surgery remain the mainstay of treatment.