Introduction to Hereditary Colorectal Cancer

Welcome to the Johns Hopkins Hereditary Colorectal Cancer Website. This site is provided to educate and inform people about hereditary colorectal cancer.  To begin, please review our overview of hereditary colorectal cancer to learn more about the involved in the various hereditary colorectal cancer syndromes.

Specific information on Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), and a gene mutation called APC I1307K may be accessed on the menu below.  We also offer information about the Hereditary Colorectal Cancer Registry as well as tailored material for children with a genetic risk for FAP.



APC I1307K    

Kid's FAP 

General Information
There are a number of different inherited conditions that have a significant risk of colon cancer. Research into these conditions and the knowledge that researchers have gained have led to the development of screening and management guidelines for both patients and their relatives. These guidelines can lead to prevention of cancer and other complications associated with these diseases.

Most colorectal cancers are sporadic, meaning that they have no prior family history of the disease. Individuals with a family history of colorectal cancer are described as having familial or hereditary colorectal cancer.

Figure 2. Distribution of colorectal cancers (flow chart).

What is Familial Colorectal Cancer?
The occurrence of colorectal cancer in more than one family member may be due to chance alone. However, it could also mean the potential for developing colorectal cancer has been passed from one generation of the family to the next generation, but the exact gene causing the cancer has not been identified. Relatives of a person with colorectal cancer may be more likely to develop it themselves.

Figure 4. Basic family pedigree

It is estimated that 15–50% of colorectal cancers are familial. A single gene, a combination of genes, or a combination of genetic and environmental factors can cause familial colorectal cancer. Typically these families have one or two members with a history of colorectal cancer or precancerous polyps.

What is Hereditary Colorectal Cancer?
We say that a family has hereditary colorectal cancer when the exact gene that causes the disease is known. Several genes that cause hereditary colorectal cancer have been identified. There may be other genes that have not yet been discovered.

If more than one person in a family has colorectal cancer, it could mean that the potential for developing this form of cancer has been passed from one generation of a family to the next generation (hereditary). In these families, relatives of people with colorectal cancer may be much more likely to develop it themselves.

Inherited colorectal cancers are associated with a genetic mutation in a cancer susceptibility gene. Everyone inherits one susceptibility gene from each of their parents, making a total of two working copies of each gene. If a mutation in one copy of a cancer susceptibility gene is passed from the parent to their child, the child is predisposed (or has the potential) to develop cancer.

The genetic causes of two hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) have been identified.

What is FAP?
Familial adenomatous polyposis (FAP) is a disorder that leads to hundreds, even thousands, of polyps in the colon and rectum at a young age, usually as a teenager or young adult. Other names for this condition are hereditary polyposis of the colorectum, familial polyposis, and Gardner’s syndrome. This condition is inherited and primarily affects the gastrointestinal tract, commonly the colon and less often the stomach and small intestine.  More on FAP                                 

What is HNPCC?
Hereditary nonpolyposis colorectal cancer (HNPCC) is also known as Lynch syndrome or cancer family syndrome. It is a condition in which the tendency to develop colorectal cancer is inherited. People with HNPCC have a 50% chance of passing the HNPCC gene to each of their children. A mutation in the genes (hMLH1 and hMSH2), that when functioning normally would protect against colon cancer, is the cause of HNPCC. People affected with this type of colorectal cancer do not develop large numbers of polyps (only a small number may be present or none at all). In families with HNPCC, cancer usually occurs on the right side of the colon. It often occurs at a younger age than colon cancer that is not inherited. Other cancers can occur in these families, including cancer of the uterus, ovaries, stomach, urinary tract, small bowel and bile ducts. 
More on HNPCC

What is APC I1307K?
About 6% of Jews whose ancestors came from Eastern Europe have an increased risk (18–30%) of developing colon cancer. This risk is much higher than the normal 5% risk. In 1997 a Johns Hopkins research team discovered an inherited gene mutation called APC I1307K. This gene increases the susceptibility for colorectal cancer.
More on APC I1307K

Click here for our downoadable educational resources on hereditary colorectal cancer syndromes.

Visit the Johns Hopkins Hereditary Colorectal Cancer Registry to see how you can help researchers learn more about hereditary colorectal cancer syndromes.