Skip to main content

COVID-19 is an emerging, rapidly evolving situation.

What people with cancer should know:

Guidance for cancer researchers:

Get the latest public health information from CDC:

Get the latest research information from NIH:

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


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.


Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.
Authors: Kho P.F. , Amant F. , Annibali D. , Ashton K. , Attia J. , Auer P.L. , Beckmann M.W. , Black A. , Brinton L. , Buchanan D.D. , et al. .
Source: International journal of cancer, 2021-01-15; 148(2), p. 307-319.
EPub date: 2020-08-07.
PMID: 32851660
Related Citations

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.
Authors: Zheng Y. , Huang T. , Wang T. , Mei Z. , Sun Z. , Zhang T. , Ellervik C. , Chai J.F. , Sim X. , van Dam R.M. , et al. .
Source: European journal of epidemiology, 2020 Jul; 35(7), p. 685-697.
EPub date: 2020-05-07.
PMID: 32383070
Related Citations

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.
Authors: Kleinstern G. , Camp N.J. , Berndt S.I. , Birmann B.M. , Nieters A. , Bracci P.M. , McKay J.D. , Ghesquières H. , Lan Q. , Hjalgrim H. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020 05; 29(5), p. 1074-1078.
EPub date: 2020-02-27.
PMID: 32108027
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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

Back to Top