The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium

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Abstract
Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28 829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)30 vs BMI−2 (OR: 1.73, 95% CI: 1.22–2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41–3.83). Older age at menarche was inversely associated with uterine sarcoma risk (15 years vs P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82–3.26) or MMMTs (OR: 2.25, 95% CI: 1.60–3.15, P-heterogeneity=0.01). In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.