Who should have genetic testing for HNPCC?

If any of the following apply to your family, you are at risk of HNPCC and genetic testing may help you and your family learn more:

1. Early onset of colorectal cancer in an individual who is less than 50 years of age
2. Two or more members in a family (first-degree relatives) with colorectal or HNPCC-related tumours*, with one of these cancers being diagnosed under the age of 50
3. Three or more members in a family with colorectal or HNPCC-related tumours*, regardless of age
4. Development of synchronous or metachronous colorectal tumours in an individual, or other HNPCC-related tumours*, regardless of age.

*HNPCC-related tumours are cancers that develop in the uterus, ovaries, stomach, biliary tract, pancreas, small bowel, urinary tract, brain and skin.

How is genetic diagnosis carried out?

Genetic diagnosis for HNPCC starts with identifying a family member who has developed cancer. A simple molecular screening test can be performed in the resected cancer tissue to look for a phenomenon known as “microsatellite instability”. If this is present, the risk of HNPCC is high and genetic testing is recommended to look for mutation in the DNA mismatch repair genes. Genetic testing only requires an aspiration of 20 ml of blood, which is a simple clinical procedure. When an HNPCC mutation is found for an individual with cancer, his/her family members can then be examined for the presence of the same mutation if they wish. This will make them aware of their own risk of cancer and provide them with an opportunity to take the appropriate prevention steps.

What do I need to do to reduce the risk of cancer if I am diagnosed with HNPCC?

There are a few simple clinical procedures that are highly effective in preventing cancer development in HNPCC gene carriers:

1. A colonoscopy is a simple screening procedure that can be done either as a day patient in a hospital or at an outpatients’ clinic. It involves passing a flexible fibre-optic tube into the anus to inspect the entire length of the large bowel. Early neoplastic changes in the colon usually manifest as polyps that are visible. These polyps can be removed during the procedure, preventing them from developing into cancer. It is recommended that HNPCC mutated gene carriers undergo a colonoscopy once every two years, starting from the age of 20-25.
2. Gynaecologic examination, transvaginal ultrasound, endometrial aspirate and blood testing for CA-125 should be performed every one to two years, starting from the age of 30-35. These are simple procedures that can be performed at an outpatients’ clinic.

There are other screening tests that may also be helpful. You should consult your doctor for further details.

 

Familial Adenomatous Polyposis (FAP) syndrome

What is Familial Adenomatous Polyposis (FAP) syndrome?

About 5% to 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 characterised by the development of hundreds to thousands of precancerous (adenomatous) colorectal polyps. These polyps usually start to develop around the age of 16, and by age 40 they may have developed into colorectal cancer.

Without appropriate treatment, almost all FAP patients will develop colorectal cancer eventually. Children of FAP patients have a 50% chance of inheriting the disease. Two-thirds of FAP patients have inherited the disease from one of their parents, and their siblings will also have a 50% chance of having the disease. For the third of FAP patients who don’t have an affected parent, the disease may have arisen due to a mutation event that occurred early in their development.

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

If you are diagnosed with FAP, each of your parents, siblings and children will have a 50% chance of having the disease. Since affected individuals may show no symptoms until the cancer develops, it’s recommended that all family members undergo regular flexible sigmoidoscopy screening, starting from age 12 to 14, to detect for the presence of polyps in the colon. With genetic testing, it’s possible to identify the disease-causing mutation in the APC gene for an FAP individual.

Genetic testing only requires taking a sample of 20 ml of blood as part of a simple clinical procedure. If the mutation is found, checks can be carried out for its presence in all family members. This allows accurate pinpointing of family members who have inherited the mutated genes, and those who have not. Family members who have not inherited the mutation will have peace of mind and will not need regular prophylactic screening. Family members who have inherited the mutation can receive appropriate prophylactic screening and cancer preventive surgery. With appropriate treatment and cancer prevention strategies, most FAP gene carriers will have a normal life span.

What is a flexible sigmoidoscopy?

A flexible sigmoidoscopy is a simple screening procedure that can be done either as a day patient in a hospital or at an outpatients’ clinic. It involves the passage of a flexible fibre-optic tube from the anus so that the rectum and sigmoid colon are visible. If polyposis is detected in the examination, a prophylactic total colectomy is needed to prevent polyps from developing into cancer. Other screening tests, such as an upper endoscopy, may be helpful for FAP families. You should consult your doctor for further details.

What treatment options are available if I have FAP?

Surgical removal of the whole colon is necessary for those who have developed polyposis, to prevent the development of cancer. Depending on the severity of the polyposis and whether there is concurrent development of rectal cancer, different surgical procedures may be suggested.

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