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Grant Details

Grant Number: 5R01CA105212-04 Interpret this number
Primary Investigator: Chen, Chu
Organization: Fred Hutchinson Cancer Research Center
Project Title: Molecular Epidemiology of Endometrial Cancer
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): It is well established that estrogen exposure increases the risk of endometrial cancer. However, the presence or absence of currently known risk factors for this disease, such as the use of unopposed estrogens or obesity, offers little sensitivity or specificity in predicting which women will go on to develop it. We propose to test the hypotheses that the risk of developing endometrial cancer is related to variation in genes that encode for enzymes: 1) involved in the biosynthesis or catabolism of estrogens, or in the response to steroid hormones, and 2) that repair DNA damage generated during estrogen exposure. A population-based case-control study of 803 endometrial cancer cases and 753 controls ages 50-74 years will be conducted in three counties of Western Washington State. This study will build upon our previous case-control study of endometrial cancer (cases=383, controls=450). We will recruit an additional 420 incident cases, diagnosed between 7/03-12/05, who are identified through a population-based cancer registry that is part of the Surveillance, Epidemiology and End Results program, and will use a subset of controls (n=303), identified through random-digit dialing from an ongoing ovarian cancer study. These controls will have intact uteri, and will be similar to the cases in terms of geographic area and age. Cases and controls will be interviewed in person regarding lifestyle and medical history, and a venous blood sample will be obtained. Genomic DNA will be tested for variants in genes involved in 1) the synthesis, catabolism, and response to estrogens; and 2) base excision repair of oxidative DNA damage and nucleotide excision repair of DNA damage caused by bulky adducts. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes and results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes, and to investigate whether the risk associated with some of the genotypes varies by other risk factors, such as exposure to exogenous hormones and obesity. Efforts will also be devoted to generating risk indices through statistical modeling that integrate potential effects of genetic variants in the estrogen metabolism pathway and/or DNA repair pathways.

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Publications

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.
Authors: Webb P.M. , Na R. , Weiderpass E. , Adami H.O. , Anderson K.E. , Bertrand K.A. , Botteri E. , Brasky T.M. , Brinton L.A. , Chen C. , et al. .
Source: Annals of oncology : official journal of the European Society for Medical Oncology, 2019-02-01; 30(2), p. 310-316.
PMID: 30566587
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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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Breastfeeding and Endometrial Cancer Risk: An Analysis From the Epidemiology of Endometrial Cancer Consortium.
Authors: Jordan S.J. , Na R. , Johnatty S.E. , Wise L.A. , Adami H.O. , Brinton L.A. , Chen C. , Cook L.S. , Dal Maso L. , De Vivo I. , et al. .
Source: Obstetrics and gynecology, 2017 06; 129(6), p. 1059-1067.
PMID: 28486362
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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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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Authors: Machiela M.J. , Zhou W. , Karlins E. , Sampson J.N. , Freedman N.D. , Yang Q. , Hicks B. , Dagnall C. , Hautman C. , Jacobs K.B. , et al. .
Source: Nature communications, 2016-06-13; 7, p. 11843.
EPub date: 2016-06-13.
PMID: 27291797
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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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Exome-wide association study of endometrial cancer in a multiethnic population.
Authors: Chen M.M. , Crous-Bou M. , Setiawan V.W. , Prescott J. , Olson S.H. , Wentzensen N. , Black A. , Brinton L. , Chen C. , Chen C. , et al. .
Source: PloS one, 2014; 9(5), p. e97045.
EPub date: 2014-05-08.
PMID: 24810602
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Type I and II endometrial cancers: have they different risk factors?
Authors: Setiawan V.W. , Yang H.P. , Pike M.C. , McCann S.E. , Yu H. , Xiang Y.B. , Wolk A. , Wentzensen N. , Weiss N.S. , Webb P.M. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013-07-10; 31(20), p. 2607-18.
EPub date: 2013-06-03.
PMID: 23733771
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Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.
Authors: Setiawan V.W. , Pike M.C. , Karageorgi S. , Deming S.L. , Anderson K. , Bernstein L. , Brinton L.A. , Cai H. , Cerhan J.R. , Cozen W. , et al. .
Source: American journal of epidemiology, 2012-08-15; 176(4), p. 269-78.
EPub date: 2012-07-23.
PMID: 22831825
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Long-term use of continuous-combined estrogen-progestin hormone therapy and risk of endometrial cancer.
Authors: Phipps A.I. , Doherty J.A. , Voigt L.F. , Hill D.A. , Beresford S.A. , Rossing M.A. , Chen C. , Weiss N.S. .
Source: Cancer causes & control : CCC, 2011 Dec; 22(12), p. 1639-46.
EPub date: 2011-09-11.
PMID: 21909949
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Polymorphisms in nucleotide excision repair genes and endometrial cancer risk.
Authors: Doherty J.A. , Weiss N.S. , Fish S. , Fan W. , Loomis M.M. , Sakoda L.C. , Rossing M.A. , Zhao L.P. , Chen C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Sep; 20(9), p. 1873-82.
EPub date: 2011-07-12.
PMID: 21750170
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Pregnancy history and risk of endometrial cancer.
Authors: Pocobelli G. , Doherty J.A. , Voigt L.F. , Beresford S.A. , Hill D.A. , Chen C. , Rossing M.A. , Holmes R.S. , Noor Z.S. , Weiss N.S. .
Source: Epidemiology (Cambridge, Mass.), 2011 Sep; 22(5), p. 638-45.
PMID: 21691206
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The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.
Authors: Lurie G. , Gaudet M.M. , Spurdle A.B. , Carney M.E. , Wilkens L.R. , Yang H.P. , Weiss N.S. , Webb P.M. , Thompson P.J. , Terada K. , et al. .
Source: PloS one, 2011-02-08; 6(2), p. e16756.
EPub date: 2011-02-08.
PMID: 21347432
Related Citations

Use of nonsteroidal antiinflammatory drugs and risk of endometrial cancer.
Authors: Bodelon C. , Doherty J.A. , Chen C. , Rossing M.A. , Weiss N.S. .
Source: American journal of epidemiology, 2009-12-15; 170(12), p. 1512-7.
EPub date: 2009-11-06.
PMID: 19897512
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Maximizing resources to study an uncommon cancer: E2C2--Epidemiology of Endometrial Cancer Consortium.
Authors: Olson S.H. , Chen C. , De Vivo I. , Doherty J.A. , Hartmuller V. , Horn-Ross P.L. , Lacey J.V. , Lynch S.M. , Sansbury L. , Setiawan V.W. , et al. .
Source: Cancer causes & control : CCC, 2009 May; 20(4), p. 491-6.
EPub date: 2009-01-09.
PMID: 19132539
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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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Endometrial cancer risk in estrogen users after switching to estrogen-progestin therapy.
Authors: Chubak J. , Doherty J.A. , Cushing-Haugen K.L. , Voigt L.F. , Saltzman B.S. , Hill D.A. , Beresford S.A. , Weiss N.S. .
Source: Cancer causes & control : CCC, 2007 Nov; 18(9), p. 1001-7.
EPub date: 2007-07-25.
PMID: 17653829
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Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.
Authors: Doherty J.A. , Cushing-Haugen K.L. , Saltzman B.S. , Voigt L.F. , Hill D.A. , Beresford S.A. , Chen C. , Weiss N.S. .
Source: American journal of obstetrics and gynecology, 2007 Aug; 197(2), p. 139.e1-7.
PMID: 17689625
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Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association.
Authors: Weiss J.M. , Weiss N.S. , Ulrich C.M. , Doherty J.A. , Chen C. .
Source: Gynecologic oncology, 2006 Dec; 103(3), p. 891-6.
EPub date: 2006-06-23.
PMID: 16806437
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Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer.
Authors: Weiss J.M. , Weiss N.S. , Ulrich C.M. , Doherty J.A. , Voigt L.F. , Chen C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 Nov; 14(11 Pt 1), p. 2524-30.
PMID: 16284373
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