Etiology

• Type I endometrial cancer: endometrioid adenocarcinomas (grade 1 and 2) derived from atypical endometrial hyperplasia

• Type II endometrial cancer: endometrioid adenocarcinomas (grade 3) and tumors of non­endometrioid histology (serous, clear cell, mucinous, squamous, transitional, and undifferentiated cells)

• Directly related to long-term exposure to increased estrogen levels

• Some genetic mutations (e.g., in the PTEN gene or mismatch repair genes) are also associated with this type of cancer.

• Mostly estrogen-independent

• Associated with endometrial atrophy (especially in postmenopausal women)

• Strongly associated with a genetic predisposition

• Nulliparity

• Early menarche and late menopause

• Polycystic ovary syndrome

• Metabolic syndrome (esp. obesity and diabetes mellitus type 2 )

• Hypertension

• Unopposed estrogen replacement therapy (e.g., for menopausal symptoms)

• History of breast cancer and tamoxifen treatment

• Lynch syndrome (hereditary nonpolyposis colorectal cancer)

Low estrogen and high progestin or progesterone levels have a protective effect.

• Multiparity

• Combination oral contraceptive pills

• Regular physical exercise

• Lifelong soy-rich diet

The most common cancer of the female genital tract in the US

• Primarily affect postmenopausal women

• Peak incidence: 65–74 years