Inherited Risk for Colorectal Cancer

About 5 to 10 percent of all colorectal cancers are caused by a heritable mutation – a genetic change that can be passed on from parent to child.

The two major subtypes of hereditary colon cancer are called familial adenomatous polyposis (FAP) and Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). In addition, some rare conditions – including attenuated familial adenomatous polyposis (AFAP) and MUTYH-associated polyposis (MAP) – have been associated with an inherited risk for colorectal cancer.

There are additional, unusual causes of hereditary colorectal cancer that will be discussed with you if your personal or family history suggests that one of these syndromes might be present.

In some families, there is a strong history of colorectal cancer although no known mutations have been detected. It is not known whether the disease susceptibility of these families occurs randomly or by hereditary mutations that have not yet been identified.

Types of Hereditary Colon Cancer

Familial Adenomatous Polyposis
Familial adenomatous polyposis (FAP) consists of many precancerous polyps — possibly hundreds or thousands — in the colon and rectum. A milder form of FAP may present with a smaller number of colorectal polyps.

Lynch Syndrome
Lynch syndrome (formerly known as hereditary nonpolyposis colorectal cancer) is associated with an increased risk of colon and rectal cancer, as well as other forms of the disease including endometrial, ovarian, gastric, urinary tract, brain, and pancreas cancers.

MYH-Associated Polyposis
MYH-associated polyposis is marked by multiple precancerous polyps in the colon and rectum, similar in number to that seen in the milder form of FAP.

Hyperplastic Polyposis Syndrome
Hyperplastic polyposis syndrome (HPS) is characterized by the development of multiple hyperplastic polyps in the colon and rectum. Currently, there is no gene mutation known to be associated with HPS.

Genetic Testing for Colorectal Cancer

A number of genetic tests are available to determine whether a person has a genetic change that predisposes him or her to colorectal cancer, including tests for MLH1, MSH2, APC, MSH6, PMS2, and MUTYH mutations. Genetic counselors and physicians can help you understand your individual cancer risk and which type of genetic tests, if any, may be useful for you or for other members of your family.

If you have a family history of colorectal cancer, we encourage you to speak to a genetic counselor – regardless of whether you would like to undergo genetic testing. We can help you understand and manage your cancer risk with or without the use of genetic tests.

Important Information for Those Who Have Had Colon Cancer Testing prior to November 2004

If you underwent genetic testing for colorectal cancer prior to November 2004, and the results were negative, you may wish to consider undergoing new tests that have become available since then.

For genetic testing of the MLH1, MSH2, and APC genes, a test called Southern blot is now available that looks for gene changes in which large portions of a gene may be missing or rearranged. There is a possibility that your previous genetic tests may not have detected such mutations, if they are present.

In addition, three genes that predispose to colorectal cancer – PMS2, MSH6, and MUTYH – have been identified in recent years, and new genetic tests are available to test for mutations in these genes.

We encourage you to call the Clinical Genetics Service at 212-434-5149 to make an appointment for further testing.

Colorectal Cancer Screening

A number of screening tests are available to find abnormal growths in the colon, called precancerous polyps, which potentially might cause colorectal cancer.

Learn more about these tests and Memorial Sloan Kettering’s guidelines for colorectal cancer screening.

Colorectal Cancer Risk Management

Each type of hereditary colorectal cancer calls for a different management strategy, but frequent monitoring is often the primary approach.

For some people at risk, surgical removal of the colon may be recommended to prevent the cancer from occurring. In some cases, doctors may recommend medications to reduce a person’s cancer risk while monitoring for signs of cancer.