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.

Public Health Relevance

Endometrial cancer is the most common gynecological cancer in the Western world and the fourth most common cancer among females in the U.S. Endometrial cancers have traditionally been divided into two major types (Type 1 and Type 2). Type 1 tumors, the most common type (~90%), have risk factors that are related to unopposed estrogen exposures (e.g. obesity and postmenopausal use of estrogen only therapy) and have favorable prognosis. Type 2 tumors are rare (~10%), but they are clinically aggressive and carry high mortality rates. At present, almost nothing is known about risk factors for Type 2. We propose a pooled analysis of more than 20 epidemiologic studies within the National Cancer Institute's Epidemiology of Endometrial Cancer Consortium (E2C2) to examine risk factors for Types 1 and 2 endometrial cancers. This large collaborative study is important because it is the only way to attain large enough sample size to study risk factors for Type 2 cancers. Our ability to fill the current void in the knowledge about risk factors for Type 2 can improve the understanding of the etiology and help design preventive strategies for these clinically aggressive and lethal cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA135632-02
Application #
7779484
Study Section
Special Emphasis Panel (ZCA1-SRRB-D (J1))
Program Officer
Mechanic, Leah E
Project Start
2009-04-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$81,125
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Olson, Sara H; De Vivo, Immaculata; Setiawan, Veronica W et al. (2015) Symposium on advances in endometrial cancer epidemiology and biology. Gynecol Oncol 138:497-500