Women's Health

Hereditary gynecological cancers: Knowing your risk


May 3, 2022

Understanding your family history will help you know if you’re at risk for certain ovarian and uterine cancers.

Most gynecological cancers are sporadic, meaning they aren’t hereditary or passed down and there’s no clear reason as to why they develop. But some gynecological cancers do result from an inherited gene mutation. Knowing your family’s medical history can help you and your doctor assess your risk for common hereditary gynecologic cancers.

“The main gynecological cancers that have a hereditary component are ovarian and uterine cancers,” explained Courtney Penn, M.D., a gynecological oncologist with Vanderbilt-Ingram Cancer Center. “And the ovarian cancer category also includes cancers of the fallopian tubes and the peritoneum.”

Most cervical cancers, Penn said, are caused by human papillomavirus. Vulva and vaginal cancers are also often caused by HPV or diseases that cause chronic inflammation, like lichen sclerosus, rather than an inherited gene mutation.

Is ovarian cancer hereditary?

“Ovarian cancer is the most common gynecologic cancer associated with an inherited gene mutation,” Penn explained. “However, most ovarian cancer cases are still considered sporadic.”

Hereditary ovarian cancer is mostly due to mutations in either the breast cancer 1 (BRCA1) or breast cancer 2 (BRCA2) gene. If you carry a mutation in one of these genes, you have what is known as Hereditary Breast and Ovarian Cancer Syndrome. With this syndrome, you have an increased risk of both breast and ovarian cancer, in addition to other cancers, such as melanoma and pancreatic cancer.

About 20% of ovarian cancers are due to a mutation in one of these genes, Penn added. But of those, 15% are due to inherited mutations. The remaining 5% of ovarian cancer cases with BRCA1 or BRCA2 gene mutations are somatic. That means the mutation developed in a patient’s tumor and is not inherited.

If you have Hereditary Breast and Ovarian Cancer Syndrome, your care provider will recommend a risk-reducing salpingo-oophorectomy, which is the removal of the ovaries and fallopian tubes. If you have BRCA1, the surgery is usually done after childbearing — at the latest between ages 35 to 40. The procedure can be delayed until age 40 to 45 if you have BRCA2, Penn said.

A small number of ovarian cancers are caused by inherited mutations in the genes RAD51C, RAD51D or BRIP1. “We generally recommend that patients who have those mutations get a risk-reducing surgery to remove their fallopian tubes and ovaries between the ages of 45 to 50,” Penn said.

Is uterine cancer genetic?

Most uterine cancers are sporadic, but up to 5% are hereditary. “Hereditary uterine cancer is usually due to Lynch syndrome,” Penn explained. “And this is due to a mutation in either MLH1, MSH2, MSH6, PMS2, or EPCAM.”

Another syndrome called Cowden can increase your risk for uterine cancer, Penn added. It is caused by a PTEN mutation.

Knowing your risk for hereditary gynecologic cancers

In some cases, your physician or a genetic counselor may recommend genetic testing — for example, if you have a personal history of a particular type of cancer or a family history of certain cancers.

The recommendation for genetic testing for hereditary gynecologic cancers based on family history depends on factors such as how many people in your family had cancer, how old they were when they were diagnosed, how those people are related to you and whether they tested positive for any genetic variants.

How family history affects hereditary gynecologic cancers

“It’s important to know your family history,” Penn said, “not just for gynecologic cancers but any cancer risk. Family history is important to help people figure out whether they need to take steps to lower their risk and lower their family members’ risk of cancer.” Talk to your doctor about your family’s history, especially if you have two or more blood relatives on the same side of the family who’ve been diagnosed with any type of cancer, Penn added.

Your ancestry may be important, as well. “For example,” Penn said, “people with Ashkenazi Jewish ancestry have an increased risk of having a BRCA1 or a BRCA2 mutation. And that’s true even if they don’t have a family history of cancer.”

Genetic testing usually involves a blood or saliva test, Penn added. “It’s really straightforward.”

Need help?

Vanderbilt Women’s Health provides care for women at all stages of their lives at locations across Middle Tennessee. Learn more here or call 615-343-5700.

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