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1. Predisposing Factors/Prevention

Risk Factors

This cancer is the fourth most common malignancy affecting women in BC, and the most common gynecologic malignancy. According to Canadian Cancer Statistics, the incidence of this cancer has been increasing over the last 30 years.

There are two types of endometrial cancer: Type 1 is characterized by an excess of estrogen, which can be attributed to obesity (conversion of androstenedione to estrone in adipose tissue), anovulatory conditions (polycystic ovarian syndrome, which results in a deficiency of progesterone), and exogenous estrogen (estrogen hormone replacement therapy, or tamoxifen, a selective estrogen receptor modulator, which acts as an estrogen agonist in the uterus). Although associated with obesity, type 2 diabetes is also an independent risk factor for Type 1 cancers, related to hyperinsulinemia. Type 1 cancers account for approximately 80-85% of all uterine cancers. They are endometrioid histology, most commonly grade 1 (well differentiated), and early stage. Approximately 15-20% of all women with Type 1 cancers are premenopausal. In general, Type 1 cancers are associated with a good prognosis, particularly if they present as Stage I, grade 1. 

Type 2 endometrial cancer is characterized by non-endometrioid histotypes, and are high-grade tumours. These include serous carcinoma (high-grade by definition in the endometrium), malignant mixed mullerian tumour (MMMT or carcinosarcoma), and clear cell carcinoma. These cancers are more likely to present at an advanced stage compared to endometrioid carcinomas. Even among those who present with Stage I disease, there is a higher likelihood of recurrence compared to endometrioid carcinomas, and therefore these patients with Type 2 cancers are often offered adjuvant chemotherapy and radiotherapy, even if they have Stage I disease. These patients do not have the same risk factors as those with Type 1 cancers. These patients with Type 2 cancers tend to be older, they are more likely to have a normal body mass index (BMI) and they do not appear to be related to an excess of estrogen.   

Endometrial cancer is also seen as part of Lynch syndrome (Hereditary non-polyposis colorectal cancer, HNPCC). This hereditary cancer syndrome is characterized by a very high lifetime risk of endometrial and colorectal cancers (both approximately 60%), as well as ovarian (lifetime risk of 10%), gastric, small bowel, ureter, and renal pelvis. This syndrome is caused by an inherited mutation in one of the DNA mismatch repair genes (mutations in MLH1, MSH2, MSH6, PMS2 account for 99% of all Lynch Syndrome), with the consequent tumors showing high microsatellite instability (MSI-H). These MSI-H tumors can be reliably identified by mismatch repair (MMR) protein immunohistochemistry. 


With respect to prevention, weight loss in obese women and improving glycemic control in diabetic women may have the most potential for reducing risk in these specific populations. The use of combination oral contraceptives has been shown to decrease risk by 50% if used for 5 or more years (1). The addition of a progestin to estrogen replacement therapy counteracts the adverse effects of unopposed estrogen on the endometrium2.

Women who are identified as having Lynch Syndrome are advised to consider risk-reducing surgery (hysterectomy and bilateral salpingo-oophorectomy) to reduce their risk of endometrial and ovarian cancers (3).  Screening for endometrial and ovarian cancer using endometrial biopsy, transvaginal ultrasound, and CA125 has not been proven to decrease the incidence or mortality from cancer in these high-risk women.


  1. Kelsey J, Whittemore AS. Epidemiology and primary prevention of cancers of the breast, endometrium and ovary: a brief review. Ann Epidemiology 1994;4:89-95. 
  2. Miller AB. Planning cancer control strategies. Chronic Dis Can 1992;13:S1-S40. 
  3. Schmeler KM et al, Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch Syndrome. N Engl J Med 2006;354(3):261-9.

SOURCE: 1. Predisposing Factors/Prevention ( )
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