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, due to defects in the genes that can be passed on to offsprings. The two main types of hereditary colorectal cancers are the Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome and the Familial Adenomatous Polyposis (FAP) syndrome, which accounts for 4% and 1% of colorectal cancers respectively. Individuals affected by the HNPCC syndrome have no symptom until cancer develop. The most important clues to suspect 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. On the other hand, patients affected by the FAP syndrome 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. The genetic defects causing these two syndromes are now known. HNPCC is caused by germline mutation in one of the DNA mismatch repair (MMR) gene. FAP is caused by germline mutation in the Adenomatous Polyposis Coli (APC) gene. It is important to note that for both types of familial colorectal cancer syndromes, cancer can be prevented by appropriate prophylactic screening or treatment. Thus, knowing whether you are affected by the disease can help you and your family members to take appropriate cancer prevention steps. Genetic diagnosis is now possible for affected patients and at risk family members. It can accurately identify individuals who carry mutation in the MMR or APC 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.

Genetic Diagnosis Service and Research

The Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory was established since 1995 and has been providing genetic diagnosis for families with familial colorectal cancer. This is a cancer prevention programme supported by the Hong Kong Cancer Fund. We are also actively performing research to understand the genetic basis of colorectal cancer. Using a state-of-the-art genetic diagnosis protocol catered for the Chinese population, we have successfully identified the causative germline MMR gene mutation for over 70 families with HNPCC syndrome, and performed genetic testing for over 250 family members. For the FAP syndrome, we have identified the causative germline mutation in over 40 families and performed genetic testing for over 150 family members. Our on-going research has shown a high incidence of early-onset colorectal cancer in Hong Kong, and a large proportion of these young patients with colorectal cancers in fact carry germline MMR gene mutation. We have identified a common founder mutation in Southern Chinese population, that originated from the Guangdong Province of China dating back to 550 to 2575 years ago. This founder mutation may accounts partly for the high incidence of early-onset colorectal cancer locally. The research data generated by our laboratory on the incidence and mutational spectrum of germline MMR gene mutation in our population and their association with early onset colorectal cancer has enabled us to formulate a rational strategy for genetic testing, management and prophylactic screening of young colorectal cancer patients and their family.

Who should undergo genetic testing?

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.