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Grant Details

Grant Number: 5R01CA091019-05 Interpret this number
Primary Investigator: Ursin, Giske
Organization: University Of Southern California
Project Title: Genes and the Estrogen Effect on Endometrial Cancer
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): The etiology of endometrial cancer is relatively well understood. Estrogen stimulation of the endometrium without the modulatory effects of progestins is the major cause. Estrogen replacement therapy (ERT) in menopause and obesity are the principal risk factors. The effect of the latter is probably due to the association between postmenopausal obesity and circulating bioavailable estrogen levels. Oral contraceptives and pregnancy, both of which deliver estrogen stimulation to the endometrium but with the continuous modulatory influence of progestins, are associated with reduction in risk. Combination hormone replacement therapy in which a progestin is added to estrogen for all or part of the monthly cycle results in no increase in endometrial cancer risk over that of a non-user of hormone replacement. Despite the fact that ERT and obesity are the major risk factors, only a small proportion of women using ERT or even with extreme obesity will develop endometrial cancer. It would be important from a public health as well as from a mechanistic view to be able to predict which women those will be. We propose to evaluate a series of eight candidate genes (CYP17, CYP19, HSD17B1, ER, CYP1A1, CYP1B1, COMT andPR) in the estrogen biosynthesis, transactivation and metabolism pathways to determine if the effects of these risk factors might be mediated or modified by genetic variability. We will evaluate this question in the context of a prospective epidemiologic study of 133,000 female California teachers (the California Teachers Study) using a nested case-control design. We will also examine in detail the possible impact of phytoestrogens on endometrial cancer risk reduction in conjunction with HRT, obesity and the eight candidate genes under evaluation.

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Publications

Identification of nine new susceptibility loci for endometrial cancer.
Authors: O'Mara T.A. , Glubb D.M. , Amant F. , Annibali D. , Ashton K. , Attia J. , Auer P.L. , Beckmann M.W. , Black A. , Bolla M.K. , et al. .
Source: Nature communications, 2018-08-09; 9(1), p. 3166.
EPub date: 2018-08-09.
PMID: 30093612
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GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer.
Authors: Chen M.M. , O'Mara T.A. , Thompson D.J. , Painter J.N. , Australian National Endometrial Cancer Study Group (ANECS) , Attia J. , Black A. , Brinton L. , Chanock S. , Chen C. , et al. .
Source: Human molecular genetics, 2016-06-15; 25(12), p. 2612-2620.
EPub date: 2016-03-23.
PMID: 27008869
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Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium.
Authors: Felix A.S. , Gaudet M.M. , La Vecchia C. , Nagle C.M. , Shu X.O. , Weiderpass E. , Adami H.O. , Beresford S. , Bernstein L. , Chen C. , et al. .
Source: International journal of cancer, 2015-03-01; 136(5), p. E410-22.
EPub date: 2014-09-30.
PMID: 25242594
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Risk factors for endometrial cancer in black and white women: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2).
Authors: Cote M.L. , Alhajj T. , Ruterbusch J.J. , Bernstein L. , Brinton L.A. , Blot W.J. , Chen C. , Gass M. , Gaussoin S. , Henderson B. , et al. .
Source: Cancer causes & control : CCC, 2015 Feb; 26(2), p. 287-296.
EPub date: 2014-12-23.
PMID: 25534916
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Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.
Authors: Prescott J. , Setiawan V.W. , Wentzensen N. , Schumacher F. , Yu H. , Delahanty R. , Bernstein L. , Chanock S.J. , Chen C. , Cook L.S. , et al. .
Source: PloS one, 2015; 10(11), p. e0143256.
EPub date: 2015-11-25.
PMID: 26606540
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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.
Authors: Setiawan V.W. , Schumacher F. , Prescott J. , Haessler J. , Malinowski J. , Wentzensen N. , Yang H. , Chanock S. , Brinton L. , Hartge P. , et al. .
Source: Carcinogenesis, 2014 Sep; 35(9), p. 2068-73.
EPub date: 2014-05-15.
PMID: 24832084
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Genome-wide association study of endometrial cancer in E2C2.
Authors: De Vivo I. , Prescott J. , Setiawan V.W. , Olson S.H. , Wentzensen N. , Australian National Endometrial Cancer Study Group , Attia J. , Black A. , Brinton L. , Chen C. , et al. .
Source: Human genetics, 2014 Feb; 133(2), p. 211-24.
EPub date: 2013-10-06.
PMID: 24096698
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Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer.
Authors: Razavi P. , Lee E. , Bernstein L. , Van Den Berg D. , Horn-Ross P.L. , Ursin G. .
Source: International journal of cancer, 2012-04-01; 130(7), p. 1629-38.
EPub date: 2011-08-17.
PMID: 21544810
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Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach.
Authors: Lee E. , Hsu C. , Haiman C.A. , Razavi P. , Horn-Ross P.L. , Van Den Berg D. , Bernstein L. , Le Marchand L. , Henderson B.E. , Setiawan V.W. , et al. .
Source: Carcinogenesis, 2010 Aug; 31(8), p. 1392-9.
EPub date: 2010-06-13.
PMID: 20547493
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Long-term postmenopausal hormone therapy and endometrial cancer.
Authors: Razavi P. , Pike M.C. , Horn-Ross P.L. , Templeman C. , Bernstein L. , Ursin G. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Feb; 19(2), p. 475-83.
EPub date: 2010-01-19.
PMID: 20086105
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Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.
Authors: Setiawan V.W. , Doherty J.A. , Shu X.O. , Akbari M.R. , Chen C. , De Vivo I. , Demichele A. , Garcia-Closas M. , Goodman M.T. , Haiman C.A. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Jan; 18(1), p. 242-7.
PMID: 19124504
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Germ line variation at 8q24 and endometrial cancer risk.
Authors: Setiawan V.W. , Ursin G. , Horn-Ross P.L. , Van Den Berg D. , Le Marchand L. , Henderson B.E. , Bernstein L. , Haiman C.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Oct; 16(10), p. 2166-8.
PMID: 17932368
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