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Grant Details

Grant Number: 5R01CA134958-02 Interpret this number
Primary Investigator: Devivo, Immaculata
Organization: Brigham And Women'S Hospital
Project Title: Genome-Wide Association Study of Endometrial Cancer
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): We propose to conduct a genome-wide association study to identify loci involved in endometrial cancer causation. We plan to utilize studies with available biospecimens, 6 cohorts from the NCI Cohort Consortium and 7 case-control studies, within the NCI Epidemiology of Endometrial Cancer Consortium, by far the largest international collaborative study of this cancer, the 4th most common in the U.S. Given the large sample size of the combined studies of whites and nonwhites, the best scientific approach to study the role of genetic variants is to pool existing studies of endometrial cancer. To this end we are proposing to conduct the initial genome- wide scan in 2,307 white cases of European descent and 2,307 matched controls using the Illumina HumanHap 610K platform. After the initial scan, we plan to genotype approximately 7,000 markers showing the strongest evidence for association with risk of endometrial cancer in a multiethnic replication sample of 3,258 cases and 3,258 matched controls. The large overall sample size and the large number of markers to be genotyped in the replication samples ensures that we will have very good power to detect the modest marginal genetic effects expected for complex diseases. We will have over 80 percent power in whites (at the genome-wide significance level of 1W10-7) to detect multiplicative odds ratios between 1.19 and 1.30 for risk allele frequencies between 10 percent and 40 percent. In the third characterization stage, we will genotype approximately 60 SNPs in those regions that achieve genome-wide significance in an additional multiethnic sample of 874 cases and 874 controls. Our sample size will also give us the unique opportunity to evaluate effect modification by known risk factors (e.g. body mass index, postmenopausal hormone use, oral contraceptive use) and assess heterogeneity in risk across ethnicity. PUBLIC HEALTH RELEVANCE: Project Narrative Endometrial cancer, the most common gynecological malignancy in the United States, has both an environmental and genetic component. To this end, we propose to conduct a genome-wide association study to identify genes involved in endometrial cancer. We plan to utilize existing studies; they include 6 cohort and 7 case control with a total sample size of 6,439 cases and 6,439 matched controls through 2007. The overall goal is to determine whether certain genotypes are predictive of future endometrial cancer risk, and whether the genotypes interact with established endometrial risk factors.

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Publications

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
Authors: Din L. , Sheikh M. , Kosaraju N. , Smedby K.E. , Bernatsky S. , Berndt S.I. , Skibola C.F. , Nieters A. , Wang S. , McKay J.D. , et al. .
Source: Genetic epidemiology, 2019 10; 43(7), p. 844-863.
EPub date: 2019-08-13.
PMID: 31407831
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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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Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies.
Authors: Mons U. , Müezzinler A. , Schöttker B. , Dieffenbach A.K. , Butterbach K. , Schick M. , Peasey A. , De Vivo I. , Trichopoulou A. , Boffetta P. , et al. .
Source: American journal of epidemiology, 2017-06-15; 185(12), p. 1317-1326.
PMID: 28459963
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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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Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.
Authors: Liu J.J. , Crous-Bou M. , Giovannucci E. , De Vivo I. .
Source: The Journal of nutrition, 2016 07; 146(7), p. 1373-8.
EPub date: 2016-06-08.
PMID: 27281805
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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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GWAS for executive function and processing speed suggests involvement of the CADM2 gene.
Authors: Ibrahim-Verbaas C.A. , Bressler J. , Debette S. , Schuur M. , Smith A.V. , Bis J.C. , Davies G. , Trompet S. , Smith J.A. , Wolf C. , et al. .
Source: Molecular psychiatry, 2016 Feb; 21(2), p. 189-197.
EPub date: 2015-04-14.
PMID: 25869804
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DNA Methylation Variants at HIF3A Locus, B-Vitamin Intake, and Long-term Weight Change: Gene-Diet Interactions in Two U.S. Cohorts.
Authors: Huang T. , Zheng Y. , Qi Q. , Xu M. , Ley S.H. , Li Y. , Kang J.H. , Wiggs J. , Pasquale L.R. , Chan A.T. , et al. .
Source: Diabetes, 2015 Sep; 64(9), p. 3146-54.
EPub date: 2015-05-22.
PMID: 26001398
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Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies.
Authors: Huang T. , Qi Q. , Zheng Y. , Ley S.H. , Manson J.E. , Hu F.B. , Qi L. .
Source: Diabetes care, 2015 Jul; 38(7), p. 1306-11.
EPub date: 2015-04-07.
PMID: 25852209
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Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.
Authors: Debette S. , Ibrahim Verbaas C.A. , Bressler J. , Schuur M. , Smith A. , Bis J.C. , Davies G. , Wolf C. , Gudnason V. , Chibnik L.B. , et al. .
Source: Biological psychiatry, 2015-04-15; 77(8), p. 749-63.
EPub date: 2014-11-25.
PMID: 25648963
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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
Authors: Zimmermann E. , Ängquist L.H. , Mirza S.S. , Zhao J.H. , Chasman D.I. , Fischer K. , Qi Q. , Smith A.V. , Thinggaard M. , Jarczok M.N. , et al. .
Source: Obesity reviews : an official journal of the International Association for the Study of Obesity, 2015 Apr; 16(4), p. 327-340.
EPub date: 2015-03-05.
PMID: 25752329
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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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Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study.
Authors: Crous-Bou M. , Fung T.T. , Prescott J. , Julin B. , Du M. , Sun Q. , Rexrode K.M. , Hu F.B. , De Vivo I. .
Source: BMJ (Clinical research ed.), 2014-12-02; 349, p. g6674.
EPub date: 2014-12-02.
PMID: 25467028
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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
Related Citations

Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies.
Authors: Qi Q. , Chu A.Y. , Kang J.H. , Huang J. , Rose L.M. , Jensen M.K. , Liang L. , Curhan G.C. , Pasquale L.R. , Wiggs J.L. , et al. .
Source: BMJ (Clinical research ed.), 2014-03-19; 348, p. g1610.
EPub date: 2014-03-19.
PMID: 24646652
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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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Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.
Authors: Ahmad S. , Rukh G. , Varga T.V. , Ali A. , Kurbasic A. , Shungin D. , Ericson U. , Koivula R.W. , Chu A.Y. , Rose L.M. , et al. .
Source: PLoS genetics, 2013; 9(7), p. e1003607.
EPub date: 2013-07-25.
PMID: 23935507
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Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.
Authors: Du M. , Prescott J. , Cornelis M.C. , Hankinson S.E. , Giovannucci E. , Kraft P. , De Vivo I. .
Source: PloS one, 2013; 8(2), p. e52240.
EPub date: 2013-02-12.
PMID: 23424613
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Epidemiologic evidence for a role of telomere dysfunction in cancer etiology.
Authors: Prescott J. , Wentzensen I.M. , Savage S.A. , De Vivo I. .
Source: Mutation research, 2012-02-01; 730(1-2), p. 75-84.
EPub date: 2011-07-02.
PMID: 21756922
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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
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