In this competing renewal, we propose to address additional questions on the role of endogenous steroid sex hormones in the development of endometrial cancer in our case-control study nested within three cohorts: the New York University Women's Health Study in New York, the Northern Sweden Health and Disease Study in Umea, Sweden, and the ORDET study in Milan, Italy. In the previous funding period we showed that the risk of endometrial cancer increased with increasing postmenopausal levels of estrogens (estradiol, estrone) and androgens (testosterone, androstenedione, DHEAS). These are the first prospective data on endogenous androgens and endometrial cancer risk. We now propose to examine endometrial cancer risk in relation to estrogen metabolites, some of which are thought to be more genotoxic than estrogens themselves, and to functional polymorphisms that impact estrogen biosynthesis, activity and metabolism. The specific hypotheses to be tested in this proposal are: (1) Circulating levels of 16alpha-hydroxyestrone are positively associated with risk of endometrial cancer, while the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone is inversely associated with risk.
This aim will be restricted to women who were postmenopausal at enrollment; (2) Functional polymorphisms in selected genes coding for enzymes involved in estrogen synthesis or metabolism (CYP17, CYP1B 1, COMT) are associated with risk of endometrial cancer; and (3) Selected polymorphisms in the progesterone receptor gene are associated with risk of endometrial cancer. There are no studies on endometrial cancer and 2- and 16alpha-hydroxyestrone, and very few studies on estrogen-related polymorphisms. We estimate that we will accrue 444 incident cases of endometrial cancer and 888 controls. We will also further evaluate the functional importance of several gene polymorphisms by examining their associations with circulating levels of estrogens and estrogen metabolites. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA081212-05
Application #
6873626
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Starks, Vaurice
Project Start
1999-04-05
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$200,688
Indirect Cost
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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Clendenen, Tess V; Rendleman, Justin; Ge, Wenzhen et al. (2015) Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology. PLoS One 10:e0135943
Clendenen, Tess; Zeleniuch-Jacquotte, Anne; Wirgin, Isaac et al. (2013) Genetic variants in hormone-related genes and risk of breast cancer. PLoS One 8:e69367
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