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Grant Details

Grant Number: 5R01CA081212-07 Interpret this number
Primary Investigator: Zeleniuch-Jacquotte, Anne
Organization: New York University School Of Medicine
Project Title: Estrogen Metabolism Related Genes & Endometrial Cancer
Fiscal Year: 2007
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DESCRIPTION (provided by applicant): 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.

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Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study.
Authors: Clendenen T.V. , Hertzmark K. , Koenig K.L. , Lundin E. , Rinaldi S. , Johnson T. , Krogh V. , Hallmans G. , Idahl A. , Lukanova A. , et al. .
Source: Hormones & cancer, 2016 06; 7(3), p. 178-87.
EPub date: 2016-02-29.
PMID: 26925952
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Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology.
Authors: Clendenen T.V. , Rendleman J. , Ge W. , Koenig K.L. , Wirgin I. , Currie D. , Shore R.E. , Kirchhoff T. , Zeleniuch-Jacquotte A. .
Source: PloS one, 2015; 10(8), p. e0135943.
EPub date: 2015-08-14.
PMID: 26274499
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Genetic variants in hormone-related genes and risk of breast cancer.
Authors: Clendenen T. , Zeleniuch-Jacquotte A. , Wirgin I. , Koenig K.L. , Afanasyeva Y. , Lundin E. , Arslan A.A. , Axelsson T. , Försti A. , Hallmans G. , et al. .
Source: PloS one, 2013; 8(7), p. e69367.
EPub date: 2013-07-23.
PMID: 23935996
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Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.
Authors: Lundin E. , Wirgin I. , Lukanova A. , Afanasyeva Y. , Krogh V. , Axelsson T. , Hemminki K. , Clendenen T.V. , Arslan A.A. , Ohlson N. , et al. .
Source: Cancer epidemiology, 2012 Oct; 36(5), p. 445-52.
EPub date: 2012-05-25.
PMID: 22633539
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Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.
Authors: Zeleniuch-Jacquotte A. , Shore R.E. , Afanasyeva Y. , Lukanova A. , Sieri S. , Koenig K.L. , Idahl A. , Krogh V. , Liu M. , Ohlson N. , et al. .
Source: British journal of cancer, 2011-10-25; 105(9), p. 1458-64.
EPub date: 2011-09-27.
PMID: 21952628
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Circulating enterolactone and risk of endometrial cancer.
Authors: Zeleniuch-Jacquotte A. , Lundin E. , Micheli A. , Koenig K.L. , Lenner P. , Muti P. , Shore R.E. , Johansson I. , Krogh V. , Lukanova A. , et al. .
Source: International journal of cancer, 2006-11-15; 119(10), p. 2376-81.
PMID: 16929490
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Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
Authors: Lukanova A. , Lundin E. , Micheli A. , Arslan A. , Ferrari P. , Rinaldi S. , Krogh V. , Lenner P. , Shore R.E. , Biessy C. , et al. .
Source: International journal of cancer, 2004-01-20; 108(3), p. 425-32.
PMID: 14648710
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Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
Authors: Lukanova A. , Zeleniuch-Jacquotte A. , Lundin E. , Micheli A. , Arslan A.A. , Rinaldi S. , Muti P. , Lenner P. , Koenig K.L. , Biessy C. , et al. .
Source: International journal of cancer, 2004-01-10; 108(2), p. 262-8.
PMID: 14639613
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