Lynch Syndrome

Lynch syndrome dramatically increases the risk for cancer in a person’s lifetime. The genetic condition can have a significant impact on individuals and families—resulting in early onset cancer, multiple cancers, and many generations of a family affected by cancer. As such, it is important to diagnose and manage Lynch syndrome in order to prevent cancer or detect it early when it is most treatable.

The Importance of Diagnosing Lynch Syndrome

Lynch syndrome has a variety of implications for individuals and families. Individuals who have Lynch syndrome have a much higher risk of developing colorectal, uterine, and other cancers than the general population. Furthermore, individuals with Lynch syndrome who already have cancer have a higher risk of developing new cancers in the future. What’s more—because Lynch syndrome is an inherited condition, it can affect other family members. A diagnosis of Lynch syndrome can shine the light on potentially increased risk throughout a family.

Diagnosing Lynch Syndrome

There is a process to diagnosing Lynch syndrome and it typically begins with a comprehensive review of the family medical history, which is sometimes followed by genetic testing.

Family History: A genetic counselor will construct a multi-generational family tree and perform a comprehensive review of a family medical history in order to assess a family’s risk of Lynch syndrome. If the family history indicates the possibility of Lynch syndrome, the counselor might suggest further tests. If you have questions and would like to speak to a genetic counselor about Lynch syndrome please either contact the UCSF cancer genetic counselors or you can find a cancer genetic counselor near you on the National Society of Genetic Counselors.

Testing: There are two types of tests used for detecting Lynch syndrome—pathology tests and genetic blood tests.
Pathology tests are tests that are performed on a tumor. When tumors are removed, most hospitals store tissue samples for many years. If Lynch syndrome is suspected, special pathology tests can be used to detect characteristics in tumors that may be caused by Lynch syndrome and can identify which gene may be responsible for Lynch syndrome in the family. There are two pathology tests used to evaluate the possibility of Lynch syndrome:

• Microsatellite instability (MSI) testing: Microsatellites are sequences of cellular DNA. In people with Lynch syndrome, tumors will show changes in the microsatellites and these changes are called microsatellite instability or MSI. Tumors with this instability are referred to as MSI-positive. Approximately 95 percent of colorectal and uterine cancers in Lynch syndrome patients are MSI-positive.
• Immunohistochemistry (IHC) testing: Immunohistochemistry testing uses special dyes to stain tissue samples in order to determine whether the proteins made by the Lynch syndrome genes are present or absent. In patients with a Lynch syndrome gene mutation, the protein will be absent in the tumor. IHC testing can help identify which of the four Lynch syndrome genes to test for. The results of IHC or MSI tests can indicate that Lynch syndrome might be present, but they don’t provide definitive information because some people can develop these gene mutations only in their cancer cells. The suspicion of Lynch syndrome will be confirmed by blood tests.

Genetic tests are tests that look for changes in your genes that indicate that you have Lynch syndrome. In order to undergo genetic testing, you will need to provide a blood or saliva sample. Genetic professionals will then perform a special laboratory analysis on your blood to look at specific gene mutations that cause Lynch syndrome.