A number of inherited mutations and cancer predisposition syndromes have been linked to gynecologic cancers, especially ovarian cancer and uterine (endometrial) cancer.
About 1.5% of women in the United States will develop ovarian cancer. Several hereditary conditions can be passed down from either parent that increase a woman’s chance of developing ovarian cancer:
- Mutations in the BRCA1 and BRCA2 genes account for approximately 5 to 15% of all ovarian cancers. Women who have these genetic mutations may have up to a 40% lifetime risk of developing ovarian cancer, specifically high-grade serous ovarian cancer.
- Lynch syndrome may give women a 20 percent lifetime risk of developing ovarian cancer, specifically endometrioid and clear cell ovarian cancers.
- BRIP1, RAD51C, and RAD51D gene mutations cause a moderately increased risk for ovarian cancer.
- PALB2 and ATM gene mutations may, based on limited evidence, be associated with a moderately increased risk for ovarian cancer.
Cancer of the uterus, also known as endometrial cancer, is the most common gynecological cancer in the United States. Women with certain hereditary syndromes may be at an increased risk of developing endometrial cancer:
- Lynch syndrome is the most common hereditary predisposition for uterine cancer. Women with Lynch syndrome may have up to a 60 percent lifetime risk of developing endometrial cancer.
- Cowden syndrome is caused by mutations in the PTEN gene. Women with Cowden syndrome may have an approximate 20 to 30% lifetime risk of developing endometrial cancer.
Other Ovarian and Uterine Tumors
Less common types of gynecological tumors have been observed in the context of certain hereditary cancer predisposition conditions, including:
- Peutz-Jeghers Syndrome (PJS) is caused by mutations in the STK11 gene. Women with PJS may be at risk of developing ovarian sex cord stromal tumors, a rare type of ovarian cancer that accounts for only 1.2% of all primary ovarian cancers.
- DICER1 gene mutations have been associated with a moderately increased risk for noncancerous and cancerous lesions in various organs. This includes Sertoli-Leydig cell tumors. These tumors of the ovaries typically develop in affected women in their teens and twenties.
- Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is caused by mutations in the FH gene. Women with HLRCC have an increased risk of developing uterine fibroids.
We recommend that women who have a hereditary gynecological cancer predisposition syndrome pursue specialized cancer surveillance examinations and possibly consider risk-reducing procedures. Individualized medical management recommendations should be discussed with a genetic counselor or doctor who is experienced in the care of people with hereditary gynecological cancer predisposition syndromes.