Study: Genes, genetic counseling and disparities in endometrial cancer

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

This study looks at the racial and ethnic differences in genetics and genetic counseling rates in a group of people with endometrial cancer to better understand disparities in outcomes. The authors tested tissue samples from a racially and ethnically diverse population of people with endometrial cancer. Their goal was to see who tested positive for an inherited mutation and whether they received genetic counseling.

Why is this study important?

Endometrial cancer is becoming more common and has few effective treatment options. Black women with endometrial cancer are two to three times less likely to survive than white women. The reasons for this are not fully known. Black women are also more likely to develop endometrial cancers that are harder to treat.

Around five to 15 percent of people with endometrial cancer test positive for an inherited mutation linked to cancer. The most common gene mutations associated with endometrial cancer are the five genes that cause Lynch syndrome (EPCAM, MLH1, MSH2, MSH6 and PMS2). Genetic counseling is recommended for people with cancer who test positive for an inherited mutation. Genetic counseling can help people understand their disease, their risk of developing other cancers and what genetic test results might mean for their relatives.

This study looked at inherited mutations in endometrial cancer: how common they are among people of different races and ethnicities, and who receives genetic counseling after testing positive. Prior research showed that Black American people with cancer are less likely to receive genetic counseling and testing. This study is the first to look specifically at race and ethnicity and inherited mutations among people with endometrial cancer.

This study used genetic testing data to better understand endometrial cancer disparities. The research team tested 1,625 people with endometrial cancer for inherited mutations linked to cancer. They looked at genetic testing results and rates of genetic counseling by self-reported race and ethnicity and Ashkenazi Jewish ancestry using these categories (sample sizes are shown in parentheses):

• Non-Hispanic white participants (1,129; 69 %))
  • Ashkenazi Jewish (202; 12 %)
  • Not Ashkenazi Jewish (927; 57%)
• Non-White participants (419; 26%)
  • Black (171; 10%)
  • Asian (124; 8%)
  • Hispanic (124; 8%)
• Participants not reporting race/ethnicity or Ashkenazi Jewish ancestry (77; 5%)

The key findings were:

• 216 (13%) of participants tested positive for an inherited mutation.
  • On average, people with an inherited mutation were diagnosed with endometrial cancer at younger ages than people without an inherited mutation.
  • The most common inherited mutations were in four of five genes that are associated with Lynch syndrome (MSH2, MSH6, MLH1, PMS2) and BRCA1 or BRCA2:
    • 39 (2.4 %) had a mutation in one of these four Lynch syndrome genes.
    • 20 (1.2 %) had a mutation in either BRCA1 or BRCA2.
    • In about half of those who tested positive for an inherited mutation, their tumor test result was not microsatellite instability high (MSI-H). In other words, looking only at tumors for signs of tumor instability may miss half of those with hereditary cancer; consideration of personal and family cancer history is also important.

• The frequency of inherited mutations was different between groups based on self-reported race, ethnicity or Ashkenazi Jewish ancestry:
  • Black participants  (7%).
  • Asian participants (12%)
  • Non-Hispanic white participants (14%)
  • Hispanic participants (12%)
  • Ashkenazi Jewish participants (20%)
• The frequency of stage IV (metastatic) disease differed between groups; Black participants were more likely to be diagnosed with stage IV  (metastatic) disease:
  • Black participants (21%).
  • Asian participants (14%)
  • Non-Hispanic white participants (11%)
  • Hispanic participants (11%)
  • Ashkenazi Jewish participants (13%).
• Black participants were twice as likely to be diagnosed with harder-to-treat tumor types:
  • 33% of Black participants had serous endometrial cancer
  • 10-15% of non-Black participants had serous endometrial cancer
• The use of genetic counseling overall was high (89%) but Black participants had the lowest rates of genetic counseling (75%).

What does this mean for me?

Experts recommend tumor testing of all endometrial cancers to look for abnormalities known as MSI-H (“microsatellite instability high") or "mismatch repair deficiency" (dMMR or MMR-D). People with Lynch syndrome are more likely to have cancers with these abnormalities.

Genetic testing is recommended for some people with endometrial cancer based on tumor test results and personal and family history of cancer. Test results may help determine treatment and provide information that can be helpful to family members. A genetic counselor can help you understand how cancer runs in families, how to talk with family members about cancer risk and the next steps for you and your family.

Some of the genes involved in endometrial cancer can also increase the risk of other cancers, including breast, colorectal, ovarian, pancreatic, prostate, skin and stomach cancers. If any of these cancers have developed in your family, ask your doctor if genetic testing or counseling is recommended for you.

It can be difficult to talk with family members about cancer. Read more about why these conversations are important and how to get started here.

Reference

Liu YL, Gordhandas S, Arora K, et al., Pathogenic germline variants in patients with endometrial cancer of diverse ancestry. Cancer; 2023; 1-12. Published online October 27, 2023.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 12/14/23