Familial Colorectal Cancers: Hereditary Non-Polyposis Colon Cancer (HNPCC)/Lynch Syndrome

Each year, about 154,000 people in the United States are diagnosed with colorectal cancer. About 5 out of 100 cases of colorectal cancers may be caused by genetic abnormalities (gene changes or mutations) that can be passed down from your parents (hereditary). One of these abnormalities is hereditary non-polyposis colon cancer (HNPCC), also called Lynch syndrome. It is the most common type of hereditary colorectal cancer and causes about 3 out of 100 cases of colorectal cancer.

There are two types of Lynch syndrome:

• Type I (HNPCC type A): Families with Lynch type I often report many cases of colorectal cancers in young (under age 50) relatives. If you have this syndrome, the average age of diagnosis of colon cancer is 44 years old. In people who don’t have this syndrome (sometimes called a sporadic cancer), the average age of diagnosis is 68 for men and 72 for women.
• Type II (HNPCC type B): Families also report colorectal cancers in young relatives. They also have cases of other HNPCC-related cancers, such as endometrial, gastric, liver, kidney, brain, and some skin cancers.

What are the criteria for having HNPCC?

The genes that have been found to cause HNPCC are MLH1, MSH2, MSH6, PMS2, and EPCAM. A mutation (change) on one of these genes means you have an 80 out of 100 lifetime risk of colon cancer.

People with HNPCC are most likely to have cancer on the right side of the colon. Sporadic cases (those not caused by a gene mutation) tend to cause cancer on the left side of the colon. Flexible sigmoidoscopy, a standard screening test for colorectal cancer, only looks at the left side of the colon and is a poor screening test for those with HNPCC.

If you have HNPCC, you develop polyps at the same rate as other people, but the polyps are more likely to turn into cancer. Polyps progress more quickly to cancer when you have HNPCC than if you have a sporadic case of colorectal cancer.

The Amsterdam II criteria help figure out if a family has a risk of HNPCC. These criteria state that HPNCC should be suspected in families when at least 3 relatives have an HNPCC-related cancer and:

• One is a first-degree relative (parent, sibling, or child) of the other two.
• At least 2 successive (2 in a row) generations are affected.
• At least 1 of these family members is diagnosed with cancer before age 50.
• FAP (Familial adenomatous polyposis) must be ruled out.
• The tumors are verified by pathology (samples looked at under a microscope).

Genetic Testing

Families that meet the Amsterdam II criteria may want to have genetic testing done. If a family member is positive for a genetic abnormality, other family members at risk can then be tested and given information about cancer screening.

It is important to remember that a negative result is not always helpful. This could mean that there is no genetic mutation causing this cancer or increasing this family’s cancer risk. However, it could also mean that the test was not able to find a mutation - even though one exists. This could happen if the family carries a mutation in a gene that has not yet been discovered or a mutation for which testing has not yet been developed.

Genetic testing can find abnormalities. There are some things you should think about when it comes to genetic testing:

• Think about how the results will affect you and your family members.
• What will a positive or negative test mean for you or others?
• What are the chances of passing the gene on to your children?
• What challenges you might face with your job and insurance coverage.

If you are thinking about genetic testing, meet with a genetic counselor.  They are trained to help patients understand genetic testing and results, and can help you make the right decision for you and your family.

Cancer Screening in HNPCC

People with HNPCC tend to develop cancers earlier and should start being screened for cancer at a younger age. Many organizations have published guidelines on cancer screening for people with HNPCC mutations, including the American College of Gastroenterology, the United States Multi-Society Task Force on Colorectal Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Recommendations from these groups are:

• To have colorectal cancer screening with colonoscopy every 1 to 2 years starting between ages 20 to 25 years, or 2 to 5 years before the earliest age of colorectal cancer diagnosis in the family – whichever comes first.
• Screening for gastric cancer with upper endoscopy starting between ages 30 to 35 years. If H. Pylori is found, it should be treated. The test should be repeated every 3 to 5 years.
• To have a yearly skin exam to look for skin cancers that have been linked to Lynch Syndrome.
• Mutation carriers who have had one or more first-degree relatives with pancreatic cancer may benefit from screening for pancreatic cancer.
• Women should have a yearly pelvic exam, pelvic ultrasound, and endometrial biopsy starting at age 30.

Talk to your provider and genetic counselor about what screening tests are right for you and at what age you should start them.

Researchers have learned more about genetic syndromes in the past 20 years with the help of patients becoming involved in research studies. If you have a family history of cancer and would like to learn more about cancer risk and research, check out the links below.

Resources for More Information

For general Lynch Syndrome (HPNCC) information visit, Lynch Syndrome International.

Find a genetic counselor in your area on the National Society of Genetic Counselors website.

Learn more about colon cancer family registries.

Learn more about screening through the Lynch Syndrome Screening Network.