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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

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.
Authors: Setiawan VW, Schumacher F, Prescott J, Haessler J, Malinowski J, Wentzensen N, Yang H, Chanock S, Brinton L, Hartge P, Lissowska J, Park SL, Cheng I, Bush WS, Crawford DC, Ursin G, Horn-Ross P, Bernstein L, Lu L, Risch H, Yu H, Sakoda LC, Doherty J, Chen C, Jackson R, Yasmeen S, Cote M, Kocarnik JM, Peters U, Kraft P, De Vivo I, Haiman CA, Kooperberg C, Le Marchand L
Source: Carcinogenesis, 2014 Sep;35(9), p. 2068-73.
EPub date: 2014 May 15.
PMID: 24832084
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Genome-wide association study of endometrial cancer in E2C2.
Authors: De Vivo I, Prescott J, Setiawan VW, Olson SH, Wentzensen N, Australian National Endometrial Cancer Study Group, Attia J, Black A, Brinton L, Chen C, Chen C, Cook LS, Crous-Bou M, Doherty J, Dunning AM, Easton DF, Friedenreich CM, Garcia-Closas M, Gaudet MM, Haiman C, Hankinson SE, Hartge P, Henderson BE, Holliday E, Horn-Ross PL, Hunter DJ, Le Marchand L, Liang X, Lissowska J, Long J, Lu L, Magliocco AM, McEvoy M, O'Mara TA, Orlow I, Painter JN, Pooler L, Rastogi R, Rebbeck TR, Risch H, Sacerdote C, Schumacher F, Scott RJ, Sheng X, Shu XO, Spurdle AB, Thompson D, Vanden Berg D, Weiss NS, Xia L, Xiang YB, Yang HP, Yu H, Zheng W, Chanock S, Kraft P
Source: Hum Genet, 2014 Feb;133(2), p. 211-24.
EPub date: 2013 Oct 6.
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 PL, Ursin G
Source: Int J Cancer, 2012 Apr 1;130(7), p. 1629-38.
EPub date: 2011 Aug 17.
PMID: 21544810
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Long-term postmenopausal hormone therapy and endometrial cancer.
Authors: Razavi P, Pike MC, Horn-Ross PL, Templeman C, Bernstein L, Ursin G
Source: Cancer Epidemiol Biomarkers Prev, 2010 Feb;19(2), p. 475-83.
EPub date: 2010 Jan 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 VW, Doherty JA, Shu XO, Akbari MR, Chen C, De Vivo I, Demichele A, Garcia-Closas M, Goodman MT, Haiman CA, Hankinson SE, Henderson BE, Horn-Ross PL, Lacey JV Jr, Le Marchand L, Levine DA, Liang X, Lissowska J, Lurie G, McGrath M, Narod SA, Rebbeck TR, Ursin G, Weiss NS, Xiang YB, Yang HP, Zheng W, Olson SH
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jan;18(1), p. 242-7.
PMID: 19124504
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Germ line variation at 8q24 and endometrial cancer risk.
Authors: Setiawan VW, Ursin G, Horn-Ross PL, Van Den Berg D, Le Marchand L, Henderson BE, Bernstein L, Haiman CA
Source: Cancer Epidemiol Biomarkers Prev, 2007 Oct;16(10), p. 2166-8.
PMID: 17932368
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