Lynch Syndrome

Diagnosis

Diagnosing Lynch syndrome usually begins with a review of your family history of cancer. Your healthcare professional will want to know whether you or anyone in your family has had colon cancer, endometrial cancer, or other cancers associated with Lynch syndrome. This may lead to additional tests and procedures.

Family history is a key factor, and genetic testing for Lynch syndrome may be considered if your family history includes:

• Multiple relatives with Lynch-associated cancers, including colon and endometrial cancer, as well as cancers of the stomach, ovaries, pancreas, kidneys, bladder, ureters, brain, gallbladder, bile ducts, small bowel, and skin
• One or more family members diagnosed with cancer before age 50
• One or more family members with more than one type of cancer
• More than one generation affected by the same type of cancer

Testing cancer cells

If you or a family member has had cancer, a sample of the cancer cells may be tested. Common tests include:

• Immunohistochemistry (IHC) testing, which uses special dyes to stain tissue samples. The presence or absence of staining indicates whether certain proteins are missing, helping determine if Lynch syndrome genes contributed to the cancer
• Microsatellite instability (MSI) testing, which looks for errors or instability in DNA sequences called microsatellites

Positive IHC or MSI results indicate that genetic changes linked to Lynch syndrome are present in the cancer cells. However, these results alone cannot confirm inherited Lynch syndrome, as some genetic changes may exist only in cancer cells.

Genetic testing

Genetic testing is used to determine whether all the cells in the body carry the genes that cause Lynch syndrome. A blood sample is typically used for this test.

• If a family member is known to have Lynch syndrome, testing may focus on the specific gene found in that family
• If you are the first in your family to be tested, a broader panel of genes may be examined to identify potential inherited risks

Genetic testing results may include:

• Positive result: A gene change causing Lynch syndrome is found, which increases your risk of certain cancers but does not mean you will definitely develop cancer. Your personal risk depends on which genes run in your family, and preventive measures or screenings can help lower this risk
• Negative result: No gene changes causing Lynch syndrome are detected, suggesting you probably do not have Lynch syndrome. However, a strong family history may still indicate an increased cancer risk
• Variant of unknown significance: Sometimes a gene change is found but its impact is unclear. A genetics professional can interpret what this means for your health

Careful evaluation and guidance from a genetics professional are important to understand your individual risk and to develop an appropriate plan for cancer prevention and monitoring.