When colon cancer is hereditary

The occurrence of colon or rectal cancer in more than one family member may be due to chance alone. However, it could mean that the potential for developing colon or rectal cancer has been passed from one generation of the family to the next generation. This means that relatives of persons with colon or rectal cancer may be more likely to develop it themselves.

ABOUT 10 PERCENT OF ALL colon or rectal cancers are hereditary. Endometrial (uterine) cancer may also occur in women from families with hereditary colorectal cancer. Several genes that are known to cause colorectal cancer have been identified. Blood tests for these genes are available and may be ordered by a doctor. Genetic counseling is strongly recommended, and in some cases required, for patients undergoing genetic testing for hereditary colorectal cancer.

Hereditary colorectal cancer syndromes include:

Familial Adenomatous Polyposis (FAP)

This disorder leads to the development of hundreds, sometimes thousands, of polyps in the colon or rectum during the teenage years. Typically, cancer develops in one or more of these polyps by age 30. The condition can also cause benign tumors of the skin, soft connective tissues and bones. It is caused by any one of several different mutations in a “tumor suppressor” gene called APC.

Familial colorectal cancer in Ashkenazi Jews

About 6 percent of Jews whose ancestors came from Eastern Europe have an 18 to 30 percent risk of developing colon cancer, far higher than the normal 5 percent risk. This increased susceptibility is due to a very specific inherited mutation of the APC gene called I1307K. Instead of affecting the function of the gene itself however, the mutation increases the odds of a second, more dangerous mutation occurring in DNA in colon cells. If that happens, cancer will occur.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

This type of colon cancer is due to mutations in genes that, when functioning normally, would protect against colon cancer. With this hereditary type of colon cancer, affected family members don’t develop a large number of polyps as a warning sign. In families with HNPCC, cancer usually occurs on the right side of the colon. It often occurs at a younger age than colon cancer which is not inherited. Other cancers can occur in these families, primarily cancer of the uterus. The two most common genes associated with HNPCC are hMLH1 and hMSH2.

Resources

Hereditary colorectal cancer registries are located throughout the United States, Canada and other countries. Registries provide patient information, referrals to experts in the management of colorectal cancer and guidance in identifying relatives at risk for the disorder.

For more information about hereditary colorectal cancer and registries, and to contact the Johns Hopkins Hereditary Colorectal Cancer Program, you can call: 410-955-4041. For an appointment in the Johns Hopkins Cancer Risk Assessment Clinic, you can call: 410-614-6319.

Dr. Bert Vogelstein is a physician at the The Johns Hopkins Oncology Center.