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 Non-polyposis Colorectal Cancer (HNPCC) syndrome, which accounts for up to 4% of colorectal cancers. The most important clues to suggest HNPCC increases the risk of cancer in more than one family member, is 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, including 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 inherited one copy from our mother and another copy from our father. The DNA mismatch repair genes normally function 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. For females with HNPCC mutation, they also have up to a 60% chance of developing endometrial (uterine) cancer by the age of 70. It is important to note that with appropriate regular prophylactic screening procedures, the majority of colorectal cancers and endometrial cancers can be prevented in HNPCC carriers. Genetic diagnosis can accurately identify individuals who carry mutation in these HNPCC genes, and can distinguish between the family members who have inherited the mutated gene and those who have not.
Who should go for genetic testing for HNPCC?
If any of the following are present in your family, you are at risk of HNPCC and genetic testing may help you and your family.

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 tumors*, with one of the 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. An individual who developed synchronous or metachronous colorectal, or other HNPCC-related tumors*, regardless of age.

*HNPCC-related tumors are cancers developing in the uterus, ovary, stomach, biliary tract, pancreas, small bowel, urinary tract, brain and skin.
How is genetic diagnosis performed?
The 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 called ¡§microsatellite instability¡¨. If it is present, the risk of HNPCC is high and genetic testing is advised to look for a 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 a HNPCC mutation is found for an individual with cancer, his/her family members can then be examined for presence of the same mutation if they wish. This will help them be aware of their own cancer risk and take 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. Colonoscopy is a simple screening procedure that can be done either as a day patient in a hospital or in an outpatient clinic. It involves the passage of a flexible fibre-optic tube from the anus to inspect the entire length of the large bowel. Early neoplastic changes in the colon usually manifest as polyps that can be seen. These polyps can be removed during the procedure, preventing their evolution into cancer. It is recommended that HNPCC mutated gene carriers should undergo a colonoscopy 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 in an outpatient clinic.

There are other screening tests that may be helpful. You should consult your doctor for details.
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 at the age of 16, and by age 40, they may have evolved into colorectal cancer. Without appropriate treatment, almost all FAP patients will develop colorectal cancer eventually. Children of FAP patients will 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 new mutation event 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 be asymptomatic until cancer develops, it is recommended that all family members undergo regular flexible sigmoidoscopy screening starting from the age of 12 to 14 to detect for the 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 taking of 20 ml of blood in a simple clinical procedure. If the mutation is found, we can check for its presence in all family members. This allows us to accurately distinguish 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 won’t 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 flexible sigmoidoscopy?
Flexible sigmoidoscopy is a simple screening procedure that can be done either as a day patient in a hospital or in an outpatient clinic. It involves the passage of a flexible fibre optic tube from the anus to make the rectum and sigmoid colon visible. If polyposis is detected in the examination, a prophylactic total colectomy is needed to prevent polyps from evolving into cancer. Other screening tests, such as an upper endoscopy, may be helpful for FAP families. You can consult your doctor for 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.

Where is help available 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 Hong Kong Cancer Fund and is totally FREE of charge. The charitable patient referral centre named "Hereditary Gastrointestinal Cancer Registry" is located in St. Paul's Hospital. The laboratory and registry will provide appropriate genetic diagnosis, genetic counselling and psychosocial support. According to your family cancer background, they will provide appropriate genetic diagnosis tests and genetic counselling. Based on the test results, they will advise you and your relatives on the appropriate preventive and screening measures to prevent cancer.

If you have any further questions, please visit their website at http://www.hku.hk/patho/colonreg, or contact the Registry Coordinator based 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: 2894-9501
Email: colonreg@hku.hk

Directors of the Laboratory and the Registry:

Prof. S.Y. Leung
Professor

YW Kan Professor in Natural Sciences
Department of Pathology
The University of Hong Kong, Queen Mary Hospital, Hong Kong

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