Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer.

According to the American Cancer Society, HNPCC accounts for 3 to 5 percent of all colorectal cancers. It develops when people are relatively young. It is indicated by polyps – but only a few, not hundreds as in familial adenomatous polyposis (FAP). Women with this condition also have a very high risk of developing cancer of the endometrium (lining of the upper part of the uterus). Other cancers associated with HNPCC include cancer of the ovary, stomach, small bowel, pancreas, kidney, ureters (tubes that carry urine from the kidneys to the bladder), and bile duct.

Doctors have found that families with HNPCC have certain characteristics:

• At least three relatives have colorectal cancer.
• Two successive generations are involved.
• At least one relative had their cancer when they were younger than age 50.
• At least two of the people are first-degree relatives.

These are called the Amsterdam criteria. If any of these hold true for your family, then you might want to seek genetic counseling. But even if your family history satisfies the Amsterdam criteria, it doesn’t mean you have HNPCC. Only about 60 percent of families who have the Amsterdam criteria have HNPCC. The other 40 percent do not; and although their colorectal cancer rate is higher than normal (about two times), it is not as high as that of people with HNPCC (about six times).

A second set of criteria for HNPCC, which has been recently revised, is called the Bethesda criteria. These are used to determine whether a person with colorectal cancer should have their cancer tested for genetic changes called microsatellite instability (MSI). These criteria include at least one of the following:

• The person is younger than 50 years.
• The person has or had another cancer (endometrial, stomach, pancreas, ovary, kidney or ureters, bile duct) that is associated with HNPCC.
• The person is younger than 60 years and the cancer has certain characteristics seen with MSI when viewed under the microscope.
• A first-degree relative has been diagnosed with a non-colorectal cancer often seen in HNPCC carriers (endometrial, stomach, pancreas, ovary, kidney, ureters, or bile duct) and is younger than 50 years.
• The person has two or more second-degree relatives who had an HNPCC-related tumor at any age.

MSI testing is the first step in laboratory testing to identify people with HNPCC. If a patient meets Bethesda criteria and has a tumor with MSI, more genetic testing will be needed to confirm that there is a mutation of one of the HNPCC genes. Still, the majority of people who meet the Bethesda criteria do not have HNPCC. On the other hand, about 2 percent of people with colorectal cancer who do not meet any of these criteria still have HNPCC when they are tested.

Doctors should also be suspicious of HNPCC if, instead of colorectal cancer, the family members have other cancers associated with this gene mutation. These are endometrial cancers, ovarian cancers, small bowel cancers, or cancer of the lining of the kidney or the ureters. Still, one family member younger than age 50 must have been diagnosed with colorectal cancer before a diagnosis of HNPCC is considered.

Accurate identification of families with these inherited syndromes is important. Then, doctors can recommend specific measures, such as screening and other preventive measures, at an early age. Because several types of cancer can be associated with inherited colorectal cancer syndromes, all people should check their family medical history for polyps or any type of cancer. Those who develop polyps or cancer should inform other family members. People with a family history of colorectal polyps or cancer should consider genetic counseling, to review their family medical tree and determine whether genetic testing may be right for them. This will help them to make decisions about getting screened and treated at an early age.

For more information about genetic screening for colorectal cancer, call Deborah Rose, MBA, Operations Director of the Familial Colorectal Cancer Registry, at 215-955-0026.