Type 1 and Type 2 Endometrial Cancer: Have They Different Risk Factors? A Pooled

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DESCRIPTION (provided by applicant): Endometrial cancer is the most common gynecological malignancy in the Western world. Based on differences in pathogenesis and clinical outcomes, endometrial cancer has been divided into two types. Type 1 tumors account for ~90% of endometrial cancers and are classified as endometrioid adenocarcinoma. The remaining Type 2 endometrial cancers are predominantly serous, clear cell, and squamous cell carcinomas. Women diagnosed with type 2 cancers have aggressive disease and poorer survival than those diagnosed with type 1 cancers. Differing somatic mutations implicated in endometrial cancer development have been reported suggesting that the two tumor groups may have distinct etiologies. At present, almost nothing is known about risk factors for Type 2 cancers. Since Type 2 cancers represent only about 10% of endometrial cancers, combining studies is the only way to attain large enough sample sizes to study their risk factors. In this study, we propose a pooled analysis of 24 epidemiologic studies (10 cohort and 14 case-control studies) within the National Cancer Institute's Epidemiology of Endometrial Cancer Consortium (E2C2) to assess the similarities and differences in risk factors for Types 1 and 2 endometrial cancers. Specifically we will examine the associations of menstrual characteristics, reproductive factors, obesity, exogenous hormone use, smoking, alcohol drinking, medical conditions, and family history of endometrial and breast cancer with invasive histologically confirmed Type 1 (n=13,000 cases) and Type 2 (n=1,100) endometrial cancers. The large sample size of the pooled analysis has the power to add unique information to the literature on endometrial cancer risk factors. In particular, this study has the ability to fill the current void in the knowledge about risk factors for the clinically aggressive and lethal Type 2 endometrial cancers.