Familial Adenomatous Polyposis (FAP) syndrome

A Guide for Patients and Families

What is Hereditary Colorectal Cancer?
In Hong Kong, more than 3500 individuals develop cancer in the large bowel every year. The large bowel includes the colon and the rectum, and hence their cancers are called colorectal cancer. Although the exact cause of colorectal cancer is still unclear, most are caused by environmental factors and occur in individuals above the age of 50. However, about 5 – 10% of colorectal cancers are hereditary. One of the diseases associated with hereditary colorectal cancer is known as Familial Adenomatous Polyposis (FAP) syndrome, which accounts for about 1% of colorectal cancers. Patients with FAP are characterized by development of hundreds to thousands of precancerous (adenomatous) colorectal polyps. These polyps usually start to develop at the age of 16, and by age 40, one of these polyps may have evolved into colorectal cancer. Without appropriate treatment, almost all FAP patients will develop colorectal cancer eventually. Children of FAP patients will have 50% chance of inheriting the disease. Two-third of FAP patients have inherited the disease from one of their parents, thus their siblings will also have 50% chance of having the disease. However, in around one-third of FAP patients, they don’t have an affected parent, and the disease may have arisen due to a new mutation event early in their development.
What causes FAP and can we prevent cancer development in FAP patients?

FAP is caused by an inherited defect (mutation) in the Adenomatous Polyposis Coli (APC) gene. We are all born with two copies of around 30,000 different genes. For each of these genes, we inherited one copy from our mother and another copy from our father. The APC gene normally functions to prevent cancer development in our colon. Individuals affected by FAP either inherit a mutated APC gene from their parents, or a new mutation may have arisen early in development. There is a 50% chance for them to pass on the disease gene to each of their off-spring. The mutation interferes with normal functioning of the gene and makes them susceptible to develop colorectal polyps and cancers. An individual with an APC gene mutation, if untreated, will have 100% life time risk of developing polyps and colorectal cancer, and 93% of the cancer will develop by the age of 50. Moreover, they are also more susceptible to develop other types of neoplastic growth, though the risk is much lower. These include gastric polyps, duodenal polyps, desmoid tumours, osteomas, cancers of the duodenum, pancreas, liver, thyroid and brain. It is important to note that with appropriate surgical treatment and regular prophylactic screening procedures, majority of colorectal cancers can be prevented in FAP gene carriers.

What can I do if I am or one of my family members is diagnosed to have FAP? How can genetic testing help my family?

If you are diagnosed to have FAP, each of your parents, siblings and children will have 50% chance of having the disease. Since affected individuals may be asymptomatic until cancer develops, it is recommended that all family members should undergo regular flexible sigmoidoscopy screening starting from the age of 12 to14 to detect for presence of polyps in the colon. With genetic testing, it is possible to identify the disease causing mutation in the APC gene for an FAP individual. Genetic testing only requires aspiration of 20 ml of blood which is a simple clinical procedure with no risk. When the mutation is found, we can check for its presence in the family members. In this way, we can accurately distinguish amongst the family members who have inherited the mutated genes and who have not. For family members who have not inherited the mutation, they can be relieved of the psychological burden and the need for regular prophylactic screening. For family members who have inherited the mutation, they can receive appropriate prophylactic screening and cancer preventive surgery. With appropriate treatment and cancer prevention strategies, most FAP gene carriers can have a normal life span.

What do I need to do to reduce cancer risk if I am a member of a FAP family?

For family members who are diagnosed as FAP gene carrier by genetic testing, or for family members who have not opt for genetic testing, they should undergo annual flexible sigmoidoscopy examination starting from the age of 12 to 14. Flexible sigmoidoscopy is a simple screening procedure that can be done either as a day-patient in a hospital or in an out-patient clinic. It involves passage of a flexible fibreoptic tube from the anus to visualize the rectum and sigmoid colon. If polyposis is detected in the examination, prophylactic total colectomy is needed to prevent evolution of the polyps into cancer.

For family members who have not inherited the mutated gene as shown by genetic testing, a baseline flexible sigmoidoscopy examination can be performed at age 15 – 20. If the sigmoidoscopy examination shows no evidence of polyposis, no further screening is needed.

There are other screening tests, such as upper endoscopy that may be helpful for FAP families. You can consult your doctor for detail.

What treatment options are available if I have FAP?

Surgical removal of the whole colon is necessary for patients who have developed polyposis, to prevent their progression into cancer. Depending on the severity of the polyposis and whether there is concurrent development of rectal cancer, different surgical procedures, including colectomy and ileorectal anastomosis, restorative proctocolectomy (pelvic pouch); or proctocolectomy may be indicated. These need to be discussed in detail with your doctor. Regular sigmoidoscopy screening of the remaining segment of ileal pouch is necessary after surgery to monitor for adenoma development and for their removal. Chemoprevention using drugs can reduce the number of polyps in the ileal pouch.

July 2006