Familial polyposis coli FAP

  What is polyposis coli (familial adenomatous polyposis or FAP)?

FAP is an inherited condition caused by a mutation in a gene that is inherited in an autosomal dominant way. This means that half the children of an affected parent will have FAP, but the remaining unaffected children do not have the gene to pass on to their offspring.

The condition is characterised by the formation of polyps, also known as adenomas (because they are at a pre-cancerous stage, where they may or may not develop into cancerous cells). By the time an affected individual is 15 to 20 years old, hundreds of adenomatous polyps will have developed in the colon.

Although each individual polyp has a fairly low risk of becoming cancer, the patient has so many polyps that colon cancer is almost inevitable by the age of 50. Commonly, this cancer occurs much earlier in adult life unless prophylactic (preventive) colectomy (the removal of the colon) is done.

Although the colon is the main site of the disease, other organs are also affected.

Individuals affected with FAP have approximately a 10 per cent lifetime risk of developing cancer in the duodenum, a cancer that is very rare in the general population.

Desmoid tumours, which are solid tumours of the connective tissues, particularly within the abdomen, occur in 5 to 10 per cent of people with FAP. Although they are not malignant, they can cause major problems by invading surrounding tissues, and they can be very difficult to cut out. Individuals with desmoid tumours have a one in five risk of death at an average age of about 35.

Benign (non-cancerous) cysts can occur on the limbs, face or scalp, and benign bony tumours of the skull and lower jawbone can also occur. Occurrence of these cysts in an individual with bowel polyps used to be known as 'Gardner's syndrome', but this is now acknowledged to be due to a mutation in the same gene that is defective in FAP, the APC (adenomatous polyposis coli) gene.

Harmless pigmented (coloured) lesions occur in the retina. These have been used as a non-invasive way of screening relatives for the disease since they tend to appear before polyps develop.

A rare form of FAP exists, known as attenuated FAP. In this condition, the mutation occurs at the extreme end of the APC gene, which, presumably, causes only a relatively minor defect in the function of the APC protein. The onset of this disease is about 10 years later than FAP, with fewer polyps (less than 100), but the risk of developing colon cancer is still very high.

What causes FAP?

FAP arises because of a mutation in the adenomatous polyposis coli (APC) gene, on chromosome no 5, which carries the instructions for the manufacture of a protein involved in the regulation of cell growth. This mutation affects one of the two copies (alleles) of the gene in every cell of the body.

When the normal copy of the gene in a cell that produces colon cells also becomes damaged by chance (and such random genetic damage occurs commonly even in the normal colon), an adenomatous polyp develops.

FAP affects about 1 in 10,000 people. Men and women are equally affected. About one-third of cases seem to arise from new mutations, which means that they will have no previous family history of the disease, but their children will still have a 50 per cent risk of being affected.

What are the symptoms?

Polyposis of the colon most commonly causes no symptoms at all but it may cause:


rectal bleeding
abdominal pain
diarrhea.

Desmoid tumours inside the abdomen cause abdominal pain and may cause an obstruction of the intestines.

How is FAP diagnosed?

Most commonly, FAP is diagnosed when a relative of a known FAP-affected individual is screened using flexible sigmoidoscopy or colonoscopy, in which the doctor looks at parts of the colon through a small tube inserted into the rectum.

Genetic diagnosis is increasingly available. This is usually done by a process known as linkage analysis, which requires blood or cells from inside the cheek collected by mouth washings from at least two other living affected family members. It detects approximately 95 per cent of cases with 98 per cent accuracy.

Eventually, the diagnosis will probably be based on identifying the gene mutation in a blood sample, but most families have different mutations and identifying all the components of the entire gene is currently a very laborious process.

What else could it be?

Usually, a firm diagnosis of FAP is not difficult to make. Occasionally, problems occur with patients with 'attenuated FAP', who have fewer polyps.

There is also an extremely rare condition called Turcot's syndrome, which is a combination of polyposis and brain tumours. It is caused by a different, as yet unidentified, gene mutation, and fewer than 100 cases have been reported worldwide.

Treatment

Children of affected parents should be screened by flexible sigmoidoscopy or colonoscopy every year from the age of 10 until the age of 35 and every three years thereafter.

Once the diagnosis of FAP is made, upper gastrointestinal endoscopy should be done every two to three years to look for duodenal disease. Once FAP has been confirmed, colon removal (colectomy) should be planned, usually by the age of 14.

Two main surgical options exist:


total removal of the colon and rectum: if the rectum is removed, the surgeon usually makes a pouch from the lower end of the small intestine (ileum) and joins it to the anus. This is a relatively complex procedure and bowel function is not normal afterwards, but it does remove colon cancer risk at the same time as avoiding a stoma bag. Individuals who have had this operation usually have about four motions per day and one at night and are likely to need to take regular antidiarrhoeal medication.


removal of the colon without removing the rectum: function is better, but the remaining rectum then needs to be surveyed regularly to see whether polyps have developed that need to be treated by polypectomy. Ultimately, the rectum may have to be removed. Regular ingestion of the non-steroidal anti-inflammatory drug (NSAID) sulindac (Clinoril) may help reduce the likelihood of polyps re-appearing in the rectum.

Treatment of lesions in the duodenum is more difficult. Some duodenal polyps can be removed by endoscopy. Extensive duodenal abnormalities can require major surgery that involves removal of a large part of the duodenum and pancreas.

Desmoid tumours inside the abdomen may need to be removed surgically, although this can be very difficult if the tumour is extensive.

What is the prognosis?

Screening techniques and surgical techniques are constantly improving, and drug therapies such as sulindac might also have an impact, so the figures we have about the outcome of the disease may be inappropriately gloomy.

We do not have accurate figures for life expectancy with appropriate screening and prophylactic colectomy. If FAP is untreated, the average survival has been estimated at 42 years. With prophylactic colectomy, the main risks to life are the development of duodenal cancer or desmoid tumours. It would be disappointing if the average life expectancy achievable now were not at least 60 years.
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