Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome

A Guide for Patients and Families

What is Hereditary Colorectal Cancer ?

In Hong Kong, more than 3200 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 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 is occurrence of cancer in more than one family member, occurrence of multiple cancers in a single individual, and onset of the 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 affected by HNPCC can inherit a mutation in one of these genes from either parent. There is also 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 an individual susceptible to develop cancers. The two most common types of can

Not all individuals carrying a HNPCC mutation will develop cancer. Individuals carrying an HNPCC mutation will have up to 80% chance of developing colorectal cancer by the age of 70. For female with HNPCC mutation, they will also have up to 60% chance of developing endometrial (uterine) cancer by the age of 70. There is an increased risk of developing other specific types of cancers as well but they are much less common (see table 1). It is important to note that with appropriate regular prophylactic screening procedures, majority of colorectal cancers and endometrial cancers can be prevented in HNPCC carriers. Thus, knowing whether you are affected by the disease can help you and your family members to take appropriate cancer prevention steps. Genetic diagnosis can accurately identify individuals who carry mutation in these HNPCC genes, and can distinguish amongst the family members who have inherited the mutated gene and who have not. For family members who have not inherited the mutation, they can be relieved of the psychological burden. For family members who have inherited the mutation, they can take appropriate cancer prevention steps.

cers caused by HNPCC mutation are colorectal cancers and endometrial (uterine) cancers.

Table 1. Risk of cancer development in individuals with HNPCC up to the age of 70 compared to the general population


General population risk



Mean age of onset




44 years

Endometrium (uterus)



46 years




56 years




42.5 years

Hepatobiliary tract



Not reported

Urinary tract



~55 years

Small bowel



49 years




~50 years

Who should go for genetic testing for HNPCC?

If any of the followings 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 tumors*, regardless of age
  4. An individual who developed synchronous or metachronous colorectal, or other HNPCC-related tumors*, regardless of age

*HNPCC-related tumors
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 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 indicated to look for mutation in the DNA mismatch repair genes. Genetic testing only requires aspiration of 20 ml of blood, which is a simple clinical procedure with no risk. 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, so as to help them knowing their own cancer risk and take appropriate prevention steps.

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

There are a few simple clinical procedures that are highly effective in pr

  • Colonoscopy 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 whole length of the large bowel. Early neoplastic changes in the colon usually manifest as polyps that can be visualized. These polyps can be removed during the procedure hence their evolution into cancer can be prevented. It is recommended that HNPCC mutated gene carriers should undergo colonoscopy every two years starting from the age of 20-25.
  • Gynaecologic examination, transvaginal ultrasound, endometrial aspirate and blood test for CA-125 should be performed every one to two years starting from the age of 30-35. These are again simple procedures that can be performed in an out-patient clinic.
eventing cancer development in HNPCC gene carriers:

There are other screening tests that may be helpful. You can consult your doctor for detail.