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Endometrial cancer genetic mutations and testing

Genetic mutations

Hereditary endometrial cancer syndromes

About 5% of women diagnosed with endometrial cancer have an inherited mutation that caused their cancer. The most common hereditary predisposition for this cancer is Lynch syndrome, which increases a woman’s lifetime risk of endometrial cancer by 17% to 60%. Lynch syndrome occurs between 1 in 300 and 1 in 3,000 people.

The second most common hereditary predisposition for endometrial cancer is Cowden syndrome, which increases a woman’s lifetime risk by 19% to 28%. The syndrome is estimated to be present in at least 1 in 200,000 people.

Source: Endometrial Cancer: Hereditary/genetic factors on the Cancer Therapy Advisor website 

DNA repair defects

Sometimes, endometrial cancer may seem to “run in a family.” We now know that some of these families have a higher risk for this cancer because they have an inherited defect in certain genes that normally help repair damage to DNA. If these repair enzymes aren’t working properly, damage to DNA is more likely to persist and cause cancer.

DNA repair defects like this have also been found in endometrial cancer cells from women who haven’t inherited them.

One of the normal genes responsible for suppressing tumor growth, called PTEN, is often abnormal in endometrial cancers. And we know that endometrial cancers without other tumor suppressor genes (or with inactive ones), like the KRAS and the TP53 gene, tend to be more likely to come back after initial treatment.

Source: “What’s New in Endometrial Cancer Research?” (American Cancer Society)

Women born with mutations in the genes linked to endometrial cancer not only have a high lifetime risk, but they’re also more likely to develop the cancer at a young age. The genes linked to endometrial cancer risk include:

Source: “Endometrial Cancer” on the FORCE (Facing our risk of cancer EMPOWERED) website

Find more about these genes, their risks, and guidelines for screening, preventing and treating cancers in people with inherited mutations in these genes:
Genes linked to Endometrial Cancer Risk

Genetic testing

Experts recommend that all endometrial cancer tumors have testing to look for an abnormality known as “mismatch repair deficiency” (dMMR) at the time of diagnosis. This abnormality is commonly found in the cancers of people with an inherited gene mutation linked to Lynch syndrome.

People with dMMR cancers are recommended to have genetic counseling and testing for an inherited mutation associated with Lynch syndrome. But not all people with dMMR cancers will test positive for a Lynch syndrome mutation. 

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 colorectal cancer gene.
  • diagnosed before age 50.
  • diagnosed with another Lynch syndrome-related cancer 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.
  • personal history of serous endometrial cancer.

For more information, see “Guidelines for genetic testing in people diagnosed with endometrial cancer” on the FORCE (Facing Hereditary Cancer Empowered) website

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