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Grant Details

Grant Number: 5R01CA098346-05 Interpret this number
Primary Investigator: Yu, Herbert
Organization: Yale University
Project Title: Role of Genetic and Lifestyle Interplay in Uterus Cancer
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): Although estrogens are believed to play a key role in the development of endometrial cancer, evidence indicates that other regulatory molecules are also involved in the disease. High-energy diets, physical inactivity, obesity, insulin resistance, and diabetes are found to be associated with the risk of endometrial cancer, and these associations cannot be explained entirely by the role of estrogens. Mitogenic growth factors are suspected to be involved in these relationships, given their possible link to these lifestyle factors, and their ability to stimulate cell proliferation, to inhibit apoptosis, and to interact synergistically with sex steroid hormones in regulating important cellular activities in sex organs. To date, there have been few epidemiologic studies addressing the role of mitogenic growth factors in endometrial cancer, especially their interplay with lifestyle factors. In this proposal, we hypothesize that certain genetic polymorphisms in the genes encoding mitogenic growth factors and molecules involved in their signal transduction pathway are associated with strong mitogenic activities; these activities synergistically interact with a lifestyle of high-energy diets and low physical activity, resulting in elevated risk for endometrial cancer. To test this hypothesis, we will carry out a population-based case-control study in the state of Connecticut. We will enroll 900 incident cases with primary endometrial cancer, aged 35-79 years, and 900 age-matched control women. Controls will be selected randomly from the state through random-digit dialing. Detailed personal information including menstrual and reproductive history, medical history, estrogen usage, dietary habits, and physical activity will be collected through in-person interview using structured questionnaires. Blood samples (buccal cells when blood is not available) will be collected for DNA analysis. Associations between polymorphisms in the proposed genes and endometrial cancer risk and their interplay with lifestyle factors will be examined using unconditional logistic regression methods. Findings of this study will provide insights into the role of mitogenic growth factors and their interaction with lifestyle factors in the etiology of endometrial cancer.

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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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Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk.
Authors: Wang Z. , Risch H. , Lu L. , Irwin M.L. , Mayne S. , Schwartz P. , Rutherford T. , De Vivo I. , Yu H. .
Source: Scientific reports, 2015-10-26; 5, p. 15582.
EPub date: 2015-10-26.
PMID: 26498156
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Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).
Authors: Yang H.P. , Cook L.S. , Weiderpass E. , Adami H.O. , Anderson K.E. , Cai H. , Cerhan J.R. , Clendenen T.V. , Felix A.S. , Friedenreich C.M. , et al. .
Source: British journal of cancer, 2015-03-03; 112(5), p. 925-33.
EPub date: 2015-02-17.
PMID: 25688738
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Disease risk estimation by combining case-control data with aggregated information on the population at risk.
Authors: Chang X. , Waagepetersen R. , Yu H. , Ma X. , Holford T.R. , Wang R. , Guan Y. .
Source: Biometrics, 2015 Mar; 71(1), p. 114-121.
EPub date: 2014-10-28.
PMID: 25351292
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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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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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The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.
Authors: Lee L.J. , Ratner E. , Uduman M. , Winter K. , Boeke M. , Greven K.M. , King S. , Burke T.W. , Underhill K. , Kim H. , et al. .
Source: PloS one, 2014; 9(4), p. e94167.
EPub date: 2014-04-14.
PMID: 24732316
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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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Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case-control study.
Authors: Arem H. , Neuhouser M.L. , Irwin M.L. , Cartmel B. , Lu L. , Risch H. , Mayne S.T. , Yu H. .
Source: European journal of nutrition, 2013 Apr; 52(3), p. 1251-60.
EPub date: 2012-08-23.
PMID: 22915050
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Polymorphisms in inflammation pathway genes and endometrial cancer risk.
Authors: Delahanty R.J. , Xiang Y.B. , Spurdle A. , Beeghly-Fadiel A. , Long J. , Thompson D. , Tomlinson I. , Yu H. , Lambrechts D. , Dörk T. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013 Feb; 22(2), p. 216-23.
EPub date: 2012-12-05.
PMID: 23221126
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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 overweight and weight gain in early adulthood in association with risk of endometrial cancer.
Authors: Lu L. , Risch H. , Irwin M.L. , Mayne S.T. , Cartmel B. , Schwartz P. , Rutherford T. , Yu H. .
Source: International journal of cancer, 2011-09-01; 129(5), p. 1237-43.
EPub date: 2011-04-25.
PMID: 21387312
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Physical activity and endometrial cancer in a population-based case-control study.
Authors: Arem H. , Irwin M.L. , Zhou Y. , Lu L. , Risch H. , Yu H. .
Source: Cancer causes & control : CCC, 2011 Feb; 22(2), p. 219-26.
EPub date: 2010-11-26.
PMID: 21110224
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IGF-II promoter specific methylation and expression in epithelial ovarian cancer and their associations with disease characteristics.
Authors: Qian B. , Katsaros D. , Lu L. , Canuto E.M. , Benedetto C. , Beeghly-Fadiel A. , Yu H. .
Source: Oncology reports, 2011 Jan; 25(1), p. 203-13.
PMID: 21109978
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Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II.
Authors: Lu L. , Katsaros D. , Shaverdashvili K. , Qian B. , Wu Y. , de la Longrais I.A. , Preti M. , Menato G. , Yu H. .
Source: European journal of cancer (Oxford, England : 1990), 2009 Aug; 45(12), p. 2212-8.
EPub date: 2009-05-26.
PMID: 19477633
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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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IGF-I in epithelial ovarian cancer and its role in disease progression.
Authors: Brokaw J. , Katsaros D. , Wiley A. , Lu L. , Su D. , Sochirca O. , de la Longrais I.A. , Mayne S. , Risch H. , Yu H. .
Source: Growth factors (Chur, Switzerland), 2007 Oct; 25(5), p. 346-54.
PMID: 18236213
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