Hereditary Nonpolyposis Colon Cancer

Diagnosis

Diagnosing HNPCC is usually a three-stage process including review of family cancer history, tumor testing, and genetic testing.

Review of Family Cancer History

To determine if a patient is at risk for HNPCC the following criteria are used:

• At least three relatives with an HNPCC-associated cancer, including colon, rectal, endometrial, small bowel, ureter or renal pelvis cancer
• One of the three relatives is a first-degree relative of the other two, such as a parent, child or sibling
• At least two generations of relatives are affected
• At least one relative is diagnosed with cancer before the age of 50
• No family history of familial adenomatous polyposis (an inherited disorder unrelated to HNPCC)

Individuals who meet the above criteria are considered to have HNPCC in their family.

Tumor Testing

Tests are done on tumors removed (even those removed years before). Tests include:

• Microsatellite instability testing — Looks for the presence of genetic instability associated with HNPCC
• Immunohistochemistry testing — Samples of tumor tissue are stained to look for the presence of proteins associated with this disease.

Genetic Testing

If the review of family cancer history and tumor testing suggest the likelihood of an HNPCC genetic mutation, the next step would be to consider having the blood test that looks for the presence or absence of an HNPCC genetic mutation.

Genetic testing is not necessary to establish a diagnosis of HNPCC and it does not always confirm the diagnosis. The decision to go forward with genetic testing is complex, however, and patients need to consult with a genetics specialist such as a genetic counselor, beforehand to discuss:

• Likelihood of finding a gene mutation
• Accuracy of genetic testing
• Medical usefulness of identifying a genetic mutation
• Medical interpretation of not finding a mutation
• Costs, waiting time for a result, and implications for insurance coverage
• Possible psychological reactions to genetic testing
• Implications for cancer prevention for the patient and their relatives

If the patient has a family member with a known HNPCC genetic mutation, and HNPCC genetic testing shows that the patient does not have that mutation, the patient can be reassured that HNPCC was not inherited. If they do not have the HNPCC gene, their risk and their children's risk for colon cancer and other HNPCC-related cancers is the same as the general population.

However, if the patient's family is considered at risk and the specific gene mutation has not yet been identified, a negative genetic test does not mean that the patient is not at risk for HNPCC. If family cancer history, tumor testing and/or genetic testing point toward HNPCC, even if genetic testing does not identify the gene mutation, the patient is still considered at risk. Researchers have discovered only four mutations known to cause HNPCC but they believe that many more exist which have yet to be discovered.

Risks for Other Cancers

Women who have HNPCC are also at increased risk for endometrial cancer (a cancer affecting the lining of the uterus). More than one in three women with HNPCC will develop endometrial cancer during their lifetimes. Women with HNPCC also have an increased risk of ovarian cancer.

People with HNPCC also have some increased risk of cancer (though much lower than the risk for developing colon or endometrial cancer) in these locations:

• Stomach
• Small intestine
• Urinary tract/bladder
• Skin
• Liver and biliary tract
• Pancreas
• Brain

Read more about genetic testing for colon and rectal cancer on
www.mayoclinic.com
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