|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|
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.
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 TV, Arslan AA, Ohlson N, Sieri S, Roy N, Koenig KL, Idahl A, Berrino F, Toniolo P, Hallmans G, Försti A, Muti P, Lenner P, Shore RE, Zeleniuch-Jacquotte A
Source: Cancer Epidemiol, 2012 Oct;36(5), p. 445-52.
EPub date: 2012 May 25.
Postmenopausal circulating levels of 2- and 16?-hydroxyestrone and risk of endometrial cancer.
Authors: Zeleniuch-Jacquotte A, Shore RE, Afanasyeva Y, Lukanova A, Sieri S, Koenig KL, Idahl A, Krogh V, Liu M, Ohlson N, Muti P, Arslan AA, Lenner P, Berrino F, Hallmans G, Toniolo P, Lundin E
Source: Br J Cancer, 2011 Oct 25;105(9), p. 1458-64.
EPub date: 2011 Sep 27.
Circulating enterolactone and risk of endometrial cancer.
Authors: Zeleniuch-Jacquotte A, Lundin E, Micheli A, Koenig KL, Lenner P, Muti P, Shore RE, Johansson I, Krogh V, Lukanova A, Stattin P, Afanasyeva Y, Rinaldi S, Arslan AA, Kaaks R, Berrino F, Hallmans G, Toniolo P, Adlercreutz H
Source: Int J Cancer, 2006 Nov 15;119(10), p. 2376-81.
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 RE, Biessy C, Muti P, Riboli E, Koenig KL, Levitz M, Stattin P, Berrino F, Hallmans G, Kaaks R, Toniolo P, Zeleniuch-Jacquotte A
Source: Int J Cancer, 2004 Jan 20;108(3), p. 425-32.
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 AA, Rinaldi S, Muti P, Lenner P, Koenig KL, Biessy C, Krogh V, Riboli E, Shore RE, Stattin P, Berrino F, Hallmans G, Toniolo P, Kaaks R
Source: Int J Cancer, 2004 Jan 10;108(2), p. 262-8.