Risk Factors for Endometrial Cancer
Risk Factors for Endometrial Cancer
Anything that increases your chance of developing cancer is called a risk factor. For endometrial cancer, the most important risk factors involve prolonged exposure to estrogen without adequate progesterone. This hormonal imbalance causes the lining of the uterus to become abnormally thick.
Having one or more risk factors does not guarantee you will develop endometrial cancer. It is also possible to develop endometrial cancer without any known risk factors. Researchers continue to learn about how endometrial cancer develops.
THE BASICS: The most significant risk factors for endometrial cancer are obesity, never having been pregnant, late menopause, early first menstrual period, estrogen-only hormone therapy, certain medical conditions, such as PCOS and diabetes, use of the drug tamoxifen, and Lynch syndrome (an inherited condition). Most risk factors for endometrial cancer are related to increased estrogen exposure.
What raises your risk for developing endometrial cancer?
Obesity. Excess body fat is the most important modifiable risk factor for endometrial cancer. Fat tissue produces estrogen, and higher levels of body fat lead to higher estrogen levels. Women with obesity have a significantly higher risk of endometrial cancer than women at a healthy weight.
Never having been pregnant. Pregnancy reduces lifetime exposure to estrogen and is protective against endometrial cancer. Women who have never been pregnant have a higher risk.
Early first menstrual period and/or late menopause. A longer lifetime of menstrual cycles means longer overall estrogen exposure.
Estrogen-only hormone therapy. Taking estrogen without progesterone after menopause significantly increases endometrial cancer risk. Adding progesterone reduces this risk.
Polycystic ovary syndrome (PCOS). PCOS is associated with irregular or absent ovulation, leading to prolonged estrogen exposure without progesterone.
Diabetes and insulin resistance. Both are associated with higher estrogen levels and increased endometrial cancer risk.
Tamoxifen use. Tamoxifen, used to treat or prevent breast cancer, acts like estrogen on the endometrium and increases the risk of endometrial cancer.
Lynch syndrome. An inherited condition caused by mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Lynch syndrome is the most important genetic risk factor for endometrial cancer and significantly increases lifetime risk.
Age. The risk of endometrial cancer increases with age. Most cases are diagnosed after menopause, with the highest incidence in women in their 60s and 70s.
Race and ethnicity. Endometrial cancer is more common in white women, but Black women are more likely to be diagnosed with high-grade or advanced-stage disease and have worse outcomes.
Prior pelvic radiation therapy. Previous radiation to the pelvis increases the risk of uterine sarcomas.
Personal or family history of endometrial cancer or Lynch-associated cancers. A personal or strong family history of endometrial, colorectal, or ovarian cancer suggests possible Lynch syndrome.
Hereditary breast and ovarian cancer syndrome (BRCA). Women with BRCA mutations, particularly BRCA1, may have a modestly increased risk of endometrial cancer, especially the serous subtype.
Factors that may lower your risk
Some factors are associated with a lower risk of endometrial cancer:
Maintaining a healthy weight through diet and exercise
Oral contraceptive use. Combined oral contraceptives reduce endometrial cancer risk
Intrauterine device (IUD). Hormonal IUDs and some copper IUDs may reduce endometrial cancer risk
Pregnancy and breastfeeding
Combined hormone therapy (estrogen plus progesterone). Unlike estrogen alone, combined hormone therapy does not increase and may decrease endometrial cancer risk.
A diet rich in fruits and vegetables and low in saturated fat may be modestly protective.