Is Testing Right for Me? I Have My Test Results


What is Hereditary Non-polyposis Colorectal Cancer?

Hereditary non-polyposis colorectal cancer, also called HNPCC or Lynch syndrome, is an inherited tendency to get colon and certain other cancers. People with HNPCC have up to an 80% (8 out of 10) chance to get colon cancer sometime in their life. They may get it at a younger age than usual. The average person in North America has 5-7% chance for colon cancer in his or her lifetime. Most cases are diagnosed between the ages of 50 and 75 years.

Women with HNPCC have a 20% to 60% chance to get endometrial cancer. Men and women with HNPCC also have a higher risk for cancers like stomach, small intestine, liver, pancreatic, gallbladder ducts, upper urinary tract, brain, skin, and prostate, but they are much less common than colon and endometrial cancer.

Everyone with HNPCC needs extra cancer screening. They should also start screening at an earlier age. See Preventing HNPCC-Related Cancers for more information. 

Rare Variations of HNPCC

Some people with HNPCC have other cancers that aren't usually linked to HNPCC. These combinations of cancers are called variants of HNPCC.

Muir-Torre Syndrome
HNPCC-linked cancers with skin tumors may be called Muir-Torre syndrome. HNPCC and Muir-Torre syndrome can be seen in the same family with the same mutation.

Turcot Syndrome
HNPCC-linked cancers with brain tumors (usually glioblastoma) may be called Turcot syndrome. Turcot syndrome can be caused by the same gene changes that cause HNPCC, but it can also be related to the gene that causes familial adenomatous polyposis (a rare inherited risk for colon cancer).
Next: Who Is At Risk for Hereditary Non-polyposis Colorectal Cancer?

Why are you considering genetic testing?

I have had cancer that has signs of HNPCC (positive MSI or immunohistochemistry test).

I have had colon or endometrial cancer, but no other testing. I'm not sure if it could be HNPCC.

I have a family member who has a gene mutation that causes HNPCC.

I have a family history with signs of HNPCC, but no one has had genetic testing yet.

None of these.

Anyone with an abnormal microsatellite instability (MSI-H) or immunohistochemistry result on tumor tissue can consider genetic testing for HNPCC. An abnormal tumor test result doesn't mean that you have HNPCC, but it does increase the chance quite a bit.

Most people with HNPCC have a mutation in either the MLH1 or MSH2. Mutations in the MSH6, PMS2, and EPCAM genes are less common. Your tumor test results may help your doctor figure out which gene(s) to test first. The first person tested usually has full gene sequencing, which looks at whole genes, "letter-by-letter," to find any change from normal. This kind of testing is expensive and time-consuming, but necessary to find as many different mutations as possible.

  • When testing finds a mutation, the result confirms that you have HNPCC. Your family members may also have HNPCC. Interested family members can have genetic testing for just the one mutation that causes your HNPCC. This is less expensive and more accurate than complete HNPCC testing.
  • When testing doesn't find a mutation, the results don't rule out that you have HNPCC or another inherited tendency to get cancer. Genetic testing cannot find all the gene mutations that cause HNPCC or other inherited cancers. You and your family members may still need to have earlier and more frequent colon cancer screening, and sometimes other tests. The same kind of genetic testing probably won't be useful for your family members.

Colon or endometrial cancer tumor screening for signs of HNPCC is the best test for people who had cancer and are concerned about HNPCC. Tumor screening can be done on tumor tissue saved after surgery. Talk to your doctor about the option of microsatellite instability (MSI) and/or immunohistochemistry (IHC) testing on your tumor. See How Tumor Screening Works for more information about these tumor screening tests.

Anyone with an abnormal tumor screening result should then consider genetic testing for HNPCC. If tumor screening is normal, genetic testing is unlikely to find a mutation. No further testing is usually recommended.

Because you have a family member with an HNPCC mutation, you have a higher chance for HNPCC-related cancers. Your risk depends on how closely related you are to someone with HNPCC. If you aren't already having extra cancer screening based on your family history, talk to your doctor about a screening plan. The only people who can safely avoid early and frequent screening are those who don't have the family mutation.

Once a mutation that causes HNPCC is found in one family member, you and other relatives can have testing for that one mutation. Testing for one mutation is usually much less expensive than complete HNPCC testing, and the results are more accurate. The laboratory will need to know the exact name of the mutation that runs in the family. If possible, it is best to give the lab a copy of a relative's genetic test results.

  • When testing finds the mutation that runs in your family, you can be sure that you have inherited HNPCC and the risk to develop colon and other cancers. Not everyone with HNPCC gets cancer. Your results don't necessarily predict your future, but they do mean that you need early and regular cancer screening.
  • When testing doesn't find a mutation, you can be sure that you did not inherit the mutation that runs in your family. Unless you have other cancer risk factors, you won't need the extra cancer screening normally recommended for people who might have HNPCC.

If your family has all of the following signs of HNPCC, you can consider testing.

  • Three cases of cancer linked to HNPCC — mainly colon, endometrial, small intestine, urinary tract, or kidney — in the family. One person should be a first-degree relative (parent, child, sibling) of the other two.
  • Spread over at least two generations.
  • With at least one family member diagnosed with cancer before age 50.

However, you may not be the best person in your family to start genetic testing. The first person in the family to have genetic testing should be someone most likely to have HNPCC. Usually this means a relative with colon or endometrial cancer at a young age or possibly more than one cancer. Ideally, tumor tissue is tested first for signs of HNPCC before genetic testing.

Genetic testing cannot find all of the mutations that cause HNPCC. Testing someone who has HNPCC first helps find out if genetic testing will be able to find the mutation that causes HNPCC in your family. It is possible to test a tumor for signs of HNPCC as long as the laboratory still has the tissue. It is also possible to do HNPCC genetic testing on DNA after a person has passed away. If a mutation is found, then all other family members can have testing for the one mutation that runs in the family, which is much less expensive and more accurate than complete gene testing. If a mutation isn't found in someone with signs of HNPCC, then testing won't be useful for anyone else in the family.

If it isn't possible to test a relative with signs of HNPCC first, you can still have testing but the meaning of your results will be less clear.

  • If testing finds a mutation, then it is likely that you have inherited HNPCC and a risk to develop colon and some other cancers. You would need earlier and more frequent cancer screening than usual. Testing can also find changes in the gene that haven't been seen before and it isn't clear if they cause HNPCC. In this case, the results don't mean that you have HNPCC but you should still have extra cancer screening.
  • When testing doesn't find a mutation, there are two possible explanations – you may not have inherited a mutation that causes HNPCC in your family or the mutation that causes HNPCC in your family cannot be found with the test that was done. In this case, a normal result doesn't change your medical care. You may still have a high risk for cancer, so you need to have frequent cancer screening starting at a young age.

If none of these situations is true for you, HNPCC genetic testing is unlikely to be useful. However, there are less common reasons for testing that aren't covered here.

There are many different causes of colon cancer. Some are genetic and most aren't. If you had cancer, a family history that concerns you, or another reason you think testing could help you, talk to your doctor or a genetic counselor.