Endometrial Cancer: Genetic Testing for Inherited Mutations

This section covers the following information about genetic testing in people diagnosed with endometrial cancer:

People with endometrial cancer should ask about genetic testing

Endometrial cancer survivors and those in treatment should speak with a genetics expert to decide if genetic testing is right for them. About 10% of people diagnosed with endometrial cancer have an inherited mutation that caused their cancer.

Genetic test results may affect your prostate cancer treatment and prognosis.

• Some genetic test results can help guide treatment decisions. People with endometrial cancer who test positive for an inherited mutation may benefit from targeted or immunotherapy to treat their cancer. 

Genetic test results may help you and your relatives understand the risk for cancer and take action to stay healthy.

• If you test positive for an inherited mutation, you may have an increased risk for other cancers.
• Expert guidelines outline cancer screening and prevention options for people at high risk for cancer due to an inherited mutation.   

Guidelines for tumor testing followed by genetic testing

Experts recommend tumor testing all endometrial cancers to look for biomarkers known as "mismatch repair deficiency" (dMMR) or microsatellite instability-High (MSI-High) at the time of diagnosis. These two related abnormalities are commonly found in the cancers of people with Lynch syndrome.

• People with dMMR/MSI-High cancers are recommended to have genetic counseling and testing for Lynch syndrome. 
  • dMMR/MSI-High cancers can occur in people who do not have Lynch syndrome. Not all people with dMMR cancers will test positive for a Lynch syndrome mutation.
  • People with inherited mutations who develop endometrial may have cancers that do not have these biomarkers. 
  • People with cancers that are not dMMR may still benefit from genetic counseling and testing. 
• Cancers with these biomarkers tend to respond well to treatment with a certain type of treatment known as immunotherapy. 

Additional guidelines for genetic testing in people diagnosed with endometrial cancer

Genetic counseling and testing for an inherited mutation is also recommended for people diagnosed with endometrial cancer who have any of the following:

• a blood relative with a known inherited mutation in a cancer gene.
• diagnosed before age 50.
• diagnosed with another type of cancer seen in people with Lynch syndrome, including colorectal, ovarian, pancreatic, stomach or other Lynch syndrome-related cancer.
• have a close relative with a Lynch syndrome-related cancer diagnosed under age 50.
• have two or more relatives with a Lynch syndrome-related cancer diagnosed at any age.

Other endometrial cancer survivors who may benefit from genetic counseling and testing

People with endometrial cancer may benefit from additional genetic counseling and expanded genetic testing if they had genetic testing in the past, tested negative, and:

• their situation matches any of the other guidelines above, and
  • they had a test that only looked for one or a few genes, or 
  • they had genetic testing before 2014. Genetic testing has improved, and laboratories can now find gene mutations that may have previously been missed.

All endometrial cancer survivors and those in treatment should speak with a genetics expert to decide if genetic testing is right for them.

Relatives of people with endometrial cancer may also benefit from testing.

Genetic counseling and testing is also recommended for anyone with the following family history of endometrial cancer:

• one or more 1st-degree relatives who has been diagnosed with endometrial cancer before age 50. 
• one or more 1st-degree relatives wo have been diagnosed with endometrial cancer and a second cancer related to Lynch syndrome (e.g., colon cancer). 
• two or more 1st- or 2nd- degree relatives who have been diagnosed with a cancer related to Lynch syndrome with at least one of the cancers diagnosed before age 50. 
• three or more 1st- or 2nd- degree relatives who have been diagnosed with a cancer related to Lynch syndrome at any age. 

Genes linked to endometrial cancer

Mutations in the following genes have been linked to increased risk for endometrial cancer.