Genetic Testing for Familial Gynecologic Cancer (Endometrial and Ovarian Cancers)

Author: Christina Bach, MBE, LCSW, OSW-C
Last Reviewed: March 14, 2023

What is Familial Gynecologic Cancer?

Gynecologic cancers affect female organs such as the uterus (endometrium), ovary, cervix, fallopian tube, vagina, or vulva.

Family history is an important part of gynecologic cancer risk. As many as 5-10% of endometrial cancers and 25% of ovarian cancers are hereditary (familial). Hereditary cancer happens when changes or mutations in genes are passed down from your parents. These genetic mutations can cause family cancer syndromes, which can lead to cancer. However, just because there seems to be a family history of cancer does not mean there is a cancer syndrome or that you will get cancer. Testing for genetic mutations is one way to get an idea of your risk of developing cancer

Endometrial and ovarian cancer can run in families.

  • Endometrial cancer can also be called “uterine” cancer. The endometrium is the innermost mucous membrane lining the uterus.
  • There is one ovary on each side of the uterus. The ovaries are glands where eggs form and where the female hormones progesterone and estrogen are made.

What are the genetic mutations linked to gynecologic cancer?

Mutations of genes are like spelling errors in the genetic code of a gene. Those who have a gene mutation may be at higher than average risk for developing certain cancers. A genetic mutation that increases the risk of gynecologic cancer is present in some families.

Genetic Mutations Linked to Endometrial Cancer

  • MLH1, MSH2, MLH3, MSH6, TGBR2, PMS1, PMS2: These gene mutations are part of a cancer syndrome called Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch Syndrome. As the name suggests, this syndrome raises your risk of colorectal cancer, but also raises your risk of developing endometrial cancer, ovarian cancer, stomach cancer, and several other cancers. (Cis)women with this syndrome have up to a 70% risk of developing endometrial cancer at some point.

Genetic Mutations Linked to Ovarian Cancer

  • BRCA1 and BRCA2: These gene mutations cause Hereditary Breast and Ovarian Cancer Syndrome (HBOC). This syndrome is linked to a higher risk of ovarian cancer, as well as breast cancer, fallopian tube cancer, and primary peritoneal cancer. There is also a higher risk of some other cancers, like pancreatic cancer and prostate cancer (only men have a prostate). Most inherited ovarian cancers are caused by mutations in BRCA1 and BRCA2 genes. A mutation in the BRCA1 gene raises a woman’s lifetime risk of ovarian cancer to between 35% and 70%. A mutation in the BRCA2 gene raises a (cis)woman’s lifetime risk of ovarian cancer to between 10% and 30%. Women in the general population without a gene mutation have less than a 2% chance of ovarian cancer.
  • MLH1, MSH2, MSH6, PMS2, and EPCAM: These gene mutations are part of a cancer syndrome called Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch Syndrome. Women with this syndrome have up to a 10% risk of developing ovarian cancer at some point.
  • STK11: This gene mutation causes a rare genetic syndrome called Peutz-Jeghers syndrome. This syndrome causes polyps in the stomach and intestines during the teenage years. People with this syndrome have a higher chance of certain cancers, including cancers of the stomach, esophagus, colon, and small intestine. Women with this syndrome have an increased risk of ovarian cancer.
  • MUTYH: This gene mutation also causes polyps in the colon and small intestine. People with this gene mutation have a higher risk of colon cancer, as well as ovary and bladder cancer.
  • ATM, BRIP1, RAD51C, RAD51D, and PALB2: These genes have been linked with ovarian cancer, as well as cancers of the breast and pancreas.

Who should have genetic testing?

In a family with a history of ovarian or endometrial cancer, the first step may be to test a family member who has had one of these cancers. If that person is found to have a harmful genetic mutation, then other family members can be tested to see if they also have the same mutation.

If you are worried you or your family may have a genetic mutation or syndrome, you may want to talk with a genetic counselor. A genetic counselor will discuss what having genetic testing can mean for you and your family. The genetic counselor will go over the risks and benefits of testing and how results will affect cancer screening and prevention recommendations for you.

It may be recommended that you schedule a visit with a genetic counselor if you have:

  • A strong family health history of breast, ovarian, or endometrial cancer.
  • A moderate family health history of breast, ovarian, or endometrial cancer and are of Ashkenazi Jewish or Eastern European ancestry (Visit CDC.gov to find out if you have an average, moderate, or strong family health history of gynecologic cancer).
  • A personal history of breast cancer and meet certain criteria (related to age at diagnosis, type of cancer, presence of certain other cancers or cancer in both breasts, ancestry, and family health history).
  • A personal history of ovarian, fallopian tube, or primary peritoneal cancer.
  • A known BRCA1, BRCA2, or other inherited mutation in your family.

Talk with your healthcare provider about your unique case and possible gene mutations. There may be other reasons for genetic counseling, or your provider may strongly recommend testing your genes even without a family history of cancer. For example, the Society of Gynecologic Oncology (SGO) has recommended that all women diagnosed with ovarian or endometrial cancer should have genetic counseling, regardless of family history.

Resources for More Information

OncoLink: Genetic Counseling and Genetic Testing

References

Johnatty, S. E., Tan, Y. Y., Buchanan, D. D., Bowman, M., Walters, R. J., Obermair, A., ... & ANECS Group. (2017). Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling. Gynecologic Oncology, 147(2), 381-387.

Kentwell, M., Dow, E., Antill, Y., Wrede, C. D., McNally, O., Higgs, E., ... & Scott, C. L. (2017). Mainstreaming cancer genetics: a model integrating germline BRCA testing into routine ovarian cancer clinics. Gynecologic Oncology, 145(1), 130-136.

McDonald, M. E., & Bender, D. P. (2019). Endometrial cancer: obesity, genetics, and targeted agents. Obstetrics and Gynecology Clinics, 46(1), 89-105.Randall, L. M., Pothuri, B., Swisher, E. M., Diaz, J. P., Buchanan, A., Witkop, C. T., ... & Lu, K. (2017). Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper. Gynecologic Oncology, 146(2), 217-224.

Ring, K. L., Garcia, C., Thomas, M. H., & Modesitt, S. C. (2017). Current and future role of genetic screening in gynecologic malignancies. American Journal of Obstetrics and Gynecology, 217(5), 512-521.

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