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Grant Details

Grant Number: 5P01CA077596-05 Interpret this number
Primary Investigator: Strom, Brian
Organization: University Of Pennsylvania
Project Title: Molecular Susceptibility to Hormone Induced Cancer
Fiscal Year: 2002


Abstract

It has long been recognized that female hormones, whether endogenous or exogenous, can be risk factors for female cancers. The overall objective of this Program is to better understand the molecular mechanisms for susceptibility to these hormone-associated cancer. In particular, hormone- mediated carcinogenesis can be seen as a multi-step process that may involve genetic regulation of the effectors of hormones, as well as somatic genetic changes subsequent to hormone exposures. This Program has mobilized investigators in pharmacoepidemiology, field epidemiology, genetic epidemiology, endocrinology, pathology, and molecular biology, to bring their talents to bear on this question, examining the relationships among hormone exposures, inherited susceptibility, and the somatic genetic sequelae of these exposures in the etiology of hormone-sensitive female cancers. This Program is composed of three Projects and four Cores. The genetic modification of hormonal exposures in breast and endometrial carcinogenesis will be studied in Projects 1 and 2. Each will use a population-based case-control study design, where hospitalized incident cases of each disease will be compared to a partially shared set of controls who will be selected randomly from the community using random digit dialing. The comparison of these two groups of cases to a group of community controls without the diseases of interest will be used to investigate risk factors for these diseases. A population-based case- control study offers several important advantages over other types of case-control studies, especially by limiting the possibility of selection bias, the major disadvantage of a non-population-based case-control study. Study subjects in both Projects will undergo a common, structured telephone interview. Particular areas of interest will be hormone exposures, family history, and reproduction-associated exposures, especially parity. In addition, cases will have their medical records reviewed as needed to validate information about their cancer. DNA bio- samples will also be collected to measures specific candidate susceptibility genotypes involved in hormone metabolism. The third Project will complement the population-based etiological studies by contributing to knowledge about molecular events associated with reproductive hormonal exposures that later breast cancer susceptibility. This study will have both an animal component and a human component. The animal component will use an established rodent model to develop and evaluate candidate genetic markers that reflect the molecular changes that occur in the breast as a result of parity. Those biomarkers identified as being of potential importance will then be evaluated further in human breast tissue, attempting to understand those parity-associated molecular changes in breast tissue that alter breast cancer susceptibility. The results from the human tissue will be analyzed in conjunction with exposure data obtained using the same questionnaire as that to be administered in Projects 1 and 2. This information will then be used to explore the basic molecular mechanisms that underlie the known epidemiologic associations between hormone-related reproductive events and breast cancers. The information resulting from this transitional study will also be useful in the future development of genetic markers, that can then be evaluated further in studies such as those in Projects 1 and 2. These three Projects will be supported by four Cores: an Administrative Core (responsible for coordination), a Hospital Network Core (responsible for hospital-based activities, including IRB approvals, case ascertainment, medical record abstraction, and specimen collection), a Field Core (responsible for identification of control subjects, recruitment of subjects into the study, questionnaire development, and administration of interviews), and a Data Management and Biostatistics Core (responsible for development and maintenance of a subject tracking system, data entry, data management, and biostatistical analysis). Each of the four Cores will serve all three of the Projects, in such a way as to maximize quality and efficiency simultaneously.



Publications

Risk factors for endometrial cancer in Black women.
Authors: Sponholtz T.R. , Palmer J.R. , Rosenberg L. , Chen C. , Chen Y. , Clarke M.A. , Clendenen T. , Du M. , Johnson L. , Liao L.M. , et al. .
Source: Cancer Causes & Control : Ccc, 2022-11-23 00:00:00.0; , .
EPub date: 2022-11-23 00:00:00.0.
PMID: 36418803
Related Citations

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.
Authors: Jordan S.J. , Na R. , Weiderpass E. , Adami H.O. , Anderson K.E. , van den Brandt P.A. , Brinton L.A. , Chen C. , Cook L.S. , Doherty J.A. , et al. .
Source: International Journal Of Cancer, 2020-10-26 00:00:00.0; , .
EPub date: 2020-10-26 00:00:00.0.
PMID: 33105052
Related Citations

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 Jun; 129(6), p. 1059-1067.
PMID: 28486362
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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. 287-96.
PMID: 25534916
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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 00:00:00.0; 31(20), p. 2607-18.
EPub date: 2013-07-10 00:00:00.0.
PMID: 23733771
Related Citations

Association Of Progesterone Receptor Gene (pgr) Variants And Breast Cancer Risk In African American Women
Authors: Gabriel C.A. , Mitra N. , Demichele A. , Rebbeck T. .
Source: Breast Cancer Research And Treatment, 2013 Jun; 139(3), p. 833-43.
PMID: 23764995
Related Citations

A genome-wide association study of breast cancer in women of African ancestry.
Authors: Chen F. , Chen G.K. , Stram D.O. , Millikan R.C. , Ambrosone C.B. , John E.M. , Bernstein L. , Zheng W. , Palmer J.R. , Hu J.J. , et al. .
Source: Human Genetics, 2013 Jan; 132(1), p. 39-48.
PMID: 22923054
Related Citations

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 00:00:00.0; 176(4), p. 269-78.
EPub date: 2012-08-15 00:00:00.0.
PMID: 22831825
Related Citations

Breast Cancer Susceptibility Polymorphisms And Endometrial Cancer Risk: A Collaborative Endometrial Cancer Study
Authors: Healey C.S. , Ahmed S. , ANECS , AOCS Management Group , O'Mara T.A. , Ferguson K. , LES , Lambrechts D. , Garcia-Dios D.A. , Vergote I. , et al. .
Source: Carcinogenesis, 2011 Dec; 32(12), p. 1862-6.
PMID: 21965274
Related Citations

Progesterone Receptor Gene Variants And Risk Of Endometrial Cancer
Authors: O'Mara T.A. , Fahey P. , Ferguson K. , Marquart L. , Lambrechts D. , Despierre E. , Vergote I. , Amant F. , Hall P. , Liu J. , et al. .
Source: Carcinogenesis, 2011 Mar; 32(3), p. 331-5.
PMID: 21148628
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 00:00:00.0; 6(2), p. e16756.
EPub date: 2011-02-08 00:00:00.0.
PMID: 21347432
Related Citations

Effect Of Hormone Metabolism Genotypes On Steroid Hormone Levels And Menopausal Symptoms In A Prospective Population-based Cohort Of Women Experiencing The Menopausal Transition
Authors: Rebbeck T.R. , Su H.I. , Sammel M.D. , Lin H. , Tran T.V. , Gracia C.R. , Freeman E.W. .
Source: Menopause (new York, N.y.), 2010 Sep-Oct; 17(5), p. 1026-34.
PMID: 20505544
Related Citations

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.
PMID: 19132539
Related Citations

Hormone-dependent Effects Of Fgfr2 And Map3k1 In Breast Cancer Susceptibility In A Population-based Sample Of Post-menopausal African-american And European-american Women
Authors: Rebbeck T.R. , DeMichele A. , Tran T.V. , Panossian S. , Bunin G.R. , Troxel A.B. , Strom B.L. .
Source: Carcinogenesis, 2009 Feb; 30(2), p. 269-74.
PMID: 19028704
Related Citations

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
Related Citations

Clique-finding For Heterogeneity And Multidimensionality In Biomarker Epidemiology Research: The Chamber Algorithm
Authors: Mushlin R.A. , Gallagher S. , Kershenbaum A. , Rebbeck T.R. .
Source: Plos One, 2009; 4(3), p. e4862.
PMID: 19287484
Related Citations

U-statistics-based Tests For Multiple Genes In Genetic Association Studies
Authors: Wei Z. , Li M. , Rebbeck T. , Li H. .
Source: Annals Of Human Genetics, 2008 Nov; 72(Pt 6), p. 821-33.
PMID: 18691161
Related Citations

Impact Of Raloxifene Or Tamoxifen Use On Endometrial Cancer Risk: A Population-based Case-control Study
Authors: DeMichele A. , Troxel A.B. , Berlin J.A. , Weber A.L. , Bunin G.R. , Turzo E. , Schinnar R. , Burgh D. , Berlin M. , Rubin S.C. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2008-09-01 00:00:00.0; 26(25), p. 4151-9.
PMID: 18757329
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Pharmacogenetic Modulation Of Combined Hormone Replacement Therapy By Progesterone-metabolism Genotypes In Postmenopausal Breast Cancer Risk
Authors: Rebbeck T.R. , Troxel A.B. , Norman S. , Bunin G. , DeMichele A. , Schinnar R. , Berlin J.A. , Strom B.L. .
Source: American Journal Of Epidemiology, 2007-12-15 00:00:00.0; 166(12), p. 1392-9.
PMID: 17827444
Related Citations

Lack Of Effect Modification Between Estrogen Metabolism Genotypes And Combined Hormone Replacement Therapy In Postmenopausal Breast Cancer Risk
Authors: Rebbeck T.R. , Troxel A.B. , Shatalova E.G. , Blanchard R. , Norman S. , Bunin G. , Demichele A. , Schinnar R. , Berlin J.A. , Strom B.L. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2007 Jun; 16(6), p. 1318-20.
PMID: 17548708
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A Retrospective Case-control Study Of The Use Of Hormone-related Supplements And Association With Breast Cancer
Authors: Rebbeck T.R. , Troxel A.B. , Norman S. , Bunin G.R. , DeMichele A. , Baumgarten M. , Berlin M. , Schinnar R. , Strom B.L. .
Source: International Journal Of Cancer, 2007-04-01 00:00:00.0; 120(7), p. 1523-8.
PMID: 17205521
Related Citations

Pairwise Combinations Of Estrogen Metabolism Genotypes In Postmenopausal Breast Cancer Etiology
Authors: Rebbeck T.R. , Troxel A.B. , Walker A.H. , Panossian S. , Gallagher S. , Shatalova E.G. , Blanchard R. , Norman S. , Bunin G. , DeMichele 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, 2007 Mar; 16(3), p. 444-50.
PMID: 17372239
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Case-control Study Of Postmenopausal Hormone Replacement Therapy And Endometrial Cancer
Authors: Strom B.L. , Schinnar R. , Weber A.L. , Bunin G. , Berlin J.A. , Baumgarten M. , DeMichele A. , Rubin S.C. , Berlin M. , Troxel A.B. , et al. .
Source: American Journal Of Epidemiology, 2006-10-15 00:00:00.0; 164(8), p. 775-86.
PMID: 16997897
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Estrogen Sulfation Genes, Hormone Replacement Therapy, And Endometrial Cancer Risk
Authors: Rebbeck T.R. , Troxel A.B. , Wang Y. , Walker A.H. , Panossian S. , Gallagher S. , Shatalova E.G. , Blanchard R. , Bunin G. , DeMichele A. , et al. .
Source: Journal Of The National Cancer Institute, 2006-09-20 00:00:00.0; 98(18), p. 1311-20.
PMID: 16985250
Related Citations

Practical Aspects Of Sharing Controls Between Case-control Studies
Authors: Bunin G.R. , Baumgarten M. , Norman S.A. , Strom B.L. , Berlin J.A. .
Source: Pharmacoepidemiology And Drug Safety, 2005 Aug; 14(8), p. 523-30.
PMID: 15959880
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Association Of Catechol-o-methyltransferase With Smoking Cessation In Two Independent Studies Of Women
Authors: Colilla S. , Lerman C. , Shields P.G. , Jepson C. , Rukstalis M. , Berlin J. , DeMichele A. , Bunin G. , Strom B.L. , Rebbeck T.R. .
Source: Pharmacogenetics And Genomics, 2005 Jun; 15(6), p. 393-8.
PMID: 15900212
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Persistent Parity-induced Changes In Growth Factors, Tgf-beta3, And Differentiation In The Rodent Mammary Gland
Authors: D'Cruz C.M. , Moody S.E. , Master S.R. , Hartman J.L. , Keiper E.A. , Imielinski M.B. , Cox J.D. , Wang J.Y. , Ha S.I. , Keister B.A. , et al. .
Source: Molecular Endocrinology (baltimore, Md.), 2002 Sep; 16(9), p. 2034-51.
PMID: 12198241
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Functional Microarray Analysis Of Mammary Organogenesis Reveals A Developmental Role In Adaptive Thermogenesis
Authors: Master S.R. , Hartman J.L. , D'Cruz C.M. , Moody S.E. , Keiper E.A. , Ha S.I. , Cox J.D. , Belka G.K. , Chodosh L.A. .
Source: Molecular Endocrinology (baltimore, Md.), 2002 Jun; 16(6), p. 1185-203.
PMID: 12040007
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A Novel Doxycycline-inducible System For The Transgenic Analysis Of Mammary Gland Biology
Authors: Gunther E.J. , Belka G.K. , Wertheim G.B. , Wang J. , Hartman J.L. , Boxer R.B. , Chodosh L.A. .
Source: Faseb Journal : Official Publication Of The Federation Of American Societies For Experimental Biology, 2002 Mar; 16(3), p. 283-92.
PMID: 11874978
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Developmental Role Of The Snf1-related Kinase Hunk In Pregnancy-induced Changes In The Mammary Gland
Authors: Gardner H.P. , Belka G.K. , Wertheim G.B. , Hartman J.L. , Ha S.I. , Gimotty P.A. , Marquis S.T. , Chodosh L.A. .
Source: Development (cambridge, England), 2000 Oct; 127(20), p. 4493-509.
PMID: 11003847
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