Proliferation of the endometrium is under the control of estrogen, and prolonged exposure to unopposed estrogen from either endogenous or exogenous sources plays a central etiologic role. Risk factors for endometrial cancer include obesity, low fertility index, early menarche, late menopause, and chronic anovulation. Granulosa cell tumors of the ovary that secrete estrogen may present with synchronous endometrial cancers. Chronic unapposed estrogen replacement increases the risk, and women taking tamoxifen for breast cancer treatment or prevention have a twofold increased risk.
The Lynch syndrome occurs in families with an autosomal dominant mutation of mismatch repair genes MLH1, MSH2, MSH6, and PMS2, which predispose to nonpolyposis colon cancer as well as endometrial and ovarian cancer. The estimated lifetime risk for endometrial cancer is 40–60%, with a mean age around 50 years. Unlike colorectal cancer, endometrial cancer risk is not lower in MSH6 mutation carriers. Most women present with stage I disease, and the survival rate is generally good (5-year survival 88%). No unique endometrial screening strategies have been established for Lynch family gene carriers.
• Impaired carbohydrate tolerance
• Late menopause
• Unopposed oestrogen therapy
• Functioning ovarian tumours
• Previous pelvic irradiation
• Family history of carcinoma of breast, ovary