Hereditary Colorectal Cancer

Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome?

What is Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome?

About 5% to 10% of colorectal cancers are hereditary. One of the most common causes of hereditary colorectal cancer is known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, which accounts for up to 4% of colorectal cancers. The most important clues which suggest HNPCC increases the risk of cancer in more than one family member are: the occurrence of multiple cancers in an individual, and the onset of cancer at an early age.

What causes HNPCC and can we prevent cancer development in HNPCC patients?

HNPCC is caused by an inherited defect (mutation) in one of the DNA mismatch repair (MMR) genes, (which include the MSH2, MLH1 and MSH6 genes). We are all born with two copies of around 30,000 different genes. For each of these genes, we inherit one copy from our mother and another copy from our father. The DNA mismatch repair genes normally work to prevent cancer development by correcting errors in our DNA.

Individuals carrying an HNPCC mutation will have up to an 80% chance of developing colorectal cancer by the age of 70. Females with an HNPCC mutation, will also have up to a 60% chance of developing endometrial (uterine) cancer by the age of 70. It’s important to note that with appropriate and regular prophylactic screening procedures, most colorectal cancers and endometrial cancers can be prevented in HNPCC carriers.

Genetic diagnosis can accurately identify individuals who carry a mutation in the HNPCC genes, and can distinguish between the family members who have inherited the mutated gene and those who have not.

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.


Hereditary Gastrointestinal Cancer

Where can I find help in Hong Kong?

The Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory of the Department of Pathology, The University of Hong Kong, Queen Mary Hospital provides a genetic diagnosis service for people with putative hereditary colorectal cancer. This cancer-prevention programme is supported by the Cancer Fund and is totally FREE of charge. The patient referral centre known as “Hereditary Gastrointestinal Cancer Registry”, is located at St. Paul’s Hospital.

Both the laboratory and the registry provide appropriate genetic diagnosis, genetic counselling and psychosocial support. According to your family cancer background, they also provide appropriate genetic diagnosis tests and genetic counselling. Based on the test results obtained, they will advise you and your relatives on appropriate preventive and screening measures.

If you have further questions concerning their services, please visit the website, or contact the Registry Coordinator at St. Paul’s Hospital:

Miss Dorothy Cheng
Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory
University Pathology Building
No.102, Pok Fu Lam Road
The University of Hong Kong
Tel: 2830-3729
Fax: 2218-5215
Email: enquiry@pathology.hku.hk

Directors of the Laboratory and the Registry:

Prof. S.Y. Leung
Professor
Department of Pathology
The University of Hong Kong, Queen Mary Hospital, Hong Kong

Dr. S.T. Yuen 
Hong Kong Cancer Fund’s Medical Advisor,
Deputy Medical Superintendent
Consultant Pathologist, Pathology Department
St Paul’s Hospital

Special thanks to