Are women with inherited gynecologic cancer susceptibility at risk for endometrial cancer?

Endometrial cancer is the fourth most common cancer in women in developed countries ¹⁰. Women with inherited gynecologic cancer susceptibility, such as Lynch syndrome or BRCA mutations, face a higher lifetime risk of developing endometrial cancer. Lynch syndrome carries up to a 60% lifetime risk ¹¹, while the risk for BRCA mutation carriers is less clear but still a concern ⁹. Understanding this risk is important for making informed decisions about surveillance and preventive surgery.

What the research says

Lynch syndrome, caused by inherited mutations in DNA mismatch repair genes like MSH2, is strongly linked to endometrial cancer. A 2025 study found that women with Lynch syndrome have up to a 60% lifetime risk of developing endometrial cancer ¹¹. In a mouse model, 50% of those with MSH2 deficiency developed endometrial cancer or precancerous lesions by 12-16 months ¹¹. For BRCA1/2 mutations, the risk of endometrial cancer is less established, but it remains an open question whether prophylactic hysterectomy (removal of the uterus) should be performed during risk-reducing surgery ⁹. A narrative review on precision prevention highlights that inherited mutations in mismatch-repair genes confer substantial risk for endometrial cancer ². Additionally, a genome-wide association study found shared genetic architecture between endometrial cancer and other gynecologic conditions, suggesting common inherited susceptibility ⁵.

What to ask your doctor

• Should I consider genetic testing for Lynch syndrome or other inherited mutations given my personal or family history?
• What is my estimated lifetime risk of endometrial cancer based on my genetic profile?
• What surveillance options are available for early detection of endometrial cancer?
• Would risk-reducing surgery, such as hysterectomy, be appropriate for me?
• How do the benefits and risks of preventive surgery compare with regular monitoring?