Abstract A114: The etiology of uterine sarcomas: A pooled analysis of the epidemiology of endometrial cancer consortium (E2C2)

Background: Uterine sarcomas, cancers that arise from connective tissue in the uterus, are extremely rare, which has limited their epidemiologic assessment. Their relatively poor prognosis, early age at diagnosis, and higher incidence among Black compared with White women, supports the need for identifying risk predictors. Accordingly, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium (E2C2). Methods: Data from five case-control and ten cohort studies were pooled, resulting in 229 uterine sarcoma cases, 7,623 endometrioid endometrial carcinoma cases (the most common form of uterine cancer), and 28,829 controls. Using multivariable polytomous logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma and endometrioid endometrial carcinoma compared to controls. Risk factors examined included body mass index (BMI), age at menarche, parity, menopausal status, menopausal hormone use, oral contraceptive (OC) use, smoking status, and history of diabetes. Similarly, we examined associations between these epidemiological factors and the two most common histological subtypes of uterine sarcoma, endometrial stromal sarcoma and leiomyosarcoma. Results: Compared with controls, significant risk factors for uterine sarcoma included obesity [BMI ≥ 30 vs. BMI < 25 kg/m2, OR (95% CI): 1.73 (1.22-2.46)] and a history of diabetes [2.31 (1.40-3.80)], while older age at menarche was inversely associated with risk [OR for age at menarche ≥ 15 years vs. < 11 years: 0.71, (0.34-1.45), p-trend: 0.0414]. Being postmenopausal, a menopausal estrogen-alone or estrogen plus progestin user, an OC user, or a current or former smoker were inversely but not significantly associated with uterine sarcoma risk. BMI was much more strongly related to endometrioid endometrial carcinomas than to uterine sarcomas (p-heterogeneity=0.0069), with a 3-fold increased risk (95% CI 2.82-3.26) found for the heaviest compared to the leanest women. Risk factor associations for histological subtypes of uterine sarcoma, endometrial stromal sarcoma (n=98) and leioyomyosarcoma (n=82), were similar to patterns observed for uterine sarcomas overall. Conclusions: In the largest epidemiological study to date of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for endometrioid endometrial carcinomas. Our results are consistent with previous reports suggesting a role for hormonal imbalances in the etiology of uterine sarcoma. Future studies with larger numbers of cases should explore additional risk factors by histological subtypes of uterine sarcoma to explain differences in age- and race-specific incidence rates. Citation Format: Ashley S. Felix, Linda S. Cook, Mia M. Gaudet, Thomas E. Rohan, Leo J. Schouten, Veronica W. Setiawan, Lauren A. Wise, Louise A. Brinton. The etiology of uterine sarcomas: A pooled analysis of the epidemiology of endometrial cancer consortium (E2C2). [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A114.