Grant Number:	5P01CA082267-05 Interpret this number
Primary Investigator:	Couch, Fergus
Organization:	Mayo Clinic Rochester
Project Title:	Epidemiologic and Genetic Studies of Breast Cancer
Fiscal Year:	2004

DESCRIPTION (Applicants Description) A P01 on the genetic epidemiology of breast cancer is proposed. It builds upon a unique resource of 426 four-to five-generation families ascertained through breast cancer patients originally ascertained between 1940 and 1952. Important observations have enriched this resource during 5 years of funding from an R01. The theme of this project is the interaction of genes and environment in the pathogenesis of this disease. These multi generation families offer distinct advantages in efforts to investigate this important subject. Project 1 seeks to I) determine the frequency of genetic alterations in BRCA1 and BRCA2 in a population-based sample of 260 families with at least two cases of breast or ovarian cancer and, II) to explore geno-environment risk interactions. Project 2 is designed to test the hypothesis that Bioactivation of estrogens, under the control of polymorphic genes, can lead to direct genotoxicity of DNA and increased risk of breast cancer. Project 3 is a genetic linkage study to identify the chromosomal location of a gene that is associated with increased mammographic breast density, a major risk factor for breast cancer. Project 4 is a follow up study of this powerful cohort of families. It seeks to investigate the natural history of mammographic breast density, and will examine important new risk factor data on adolescent diet and early life exposures. In addition, this follow-up survey will ascertain additional breast cancer cases for Projects 1 and 2. The projects are supported by four cores that are essential to carry out the overall P01: administration, biostatistics, mammography, and epidemiology. The investigative team is multidisciplinary, experienced, and brings a history of productive collaborations. The findings from this important project could be critical to our understanding of the genetic epidemiology of breast cancer.




Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.
Authors: Darabi H. , McCue K. , Beesley J. , Michailidou K. , Nord S. , Kar S. , Humphreys K. , Thompson D. , Ghoussaini M. , Bolla M.K. , et al. .
Source: American journal of human genetics, 2015-07-02; 97(1), p. 22-34.
EPub date: 2015-06-11.
PMID: 26073781
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Linkage analysis of obesity phenotypes in pre- and post-menopausal women from a United States mid-western population.
Authors: Kelemen L.E. , Atkinson E.J. , de Andrade M. , Pankratz V.S. , Cunningham J.M. , Wang A. , Hilker C.A. , Couch F.J. , Sellers T.A. , Vachon C.M. .
Source: BMC medical genetics, 2010-11-09; 11, p. 156.
EPub date: 2010-11-09.
PMID: 21062459
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Texture features from mammographic images and risk of breast cancer.
Authors: Manduca A. , Carston M.J. , Heine J.J. , Scott C.G. , Pankratz V.S. , Brandt K.R. , Sellers T.A. , Vachon C.M. , Cerhan J.R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Mar; 18(3), p. 837-45.
EPub date: 2009-03-03.
PMID: 19258482
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Adult daughters' reports of breast cancer risk reduction and early detection advice received from their mothers: an exploratory study.
Authors: Sinicrope P.S. , Patten C.A. , Clark L.P. , Brockman T.A. , Rock E.E. , Frost M.H. , Petersen L.R. , Vierkant R.A. , Vachon C.M. , Fredericksen Z.S. , et al. .
Source: Psycho-oncology, 2009 Feb; 18(2), p. 169-78.
PMID: 18636437
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Familial and perceived risk of breast cancer in relation to use of complementary medicine.
Authors: Myers C.D. , Jacobsen P.B. , Huang Y. , Frost M.H. , Patten C.A. , Cerhan J.R. , Sellers T.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Jun; 17(6), p. 1527-34.
EPub date: 2008-06-09.
PMID: 18541615
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Age-specific trends in mammographic density: the Minnesota Breast Cancer Family Study.
Authors: Kelemen L.E. , Pankratz V.S. , Sellers T.A. , Brandt K.R. , Wang A. , Janney C. , Fredericksen Z.S. , Cerhan J.R. , Vachon C.M. .
Source: American journal of epidemiology, 2008-05-01; 167(9), p. 1027-36.
EPub date: 2008-04-02.
PMID: 18385204
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Strong evidence of a genetic determinant for mammographic density, a major risk factor for breast cancer.
Authors: Vachon C.M. , Sellers T.A. , Carlson E.E. , Cunningham J.M. , Hilker C.A. , Smalley R.L. , Schaid D.J. , Kelemen L.E. , Couch F.J. , Pankratz V.S. .
Source: Cancer research, 2007-09-01; 67(17), p. 8412-8.
PMID: 17804758
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A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches.
Authors: Olson J.E. , Ingle J.N. , Ma C.X. , Pelleymounter L.L. , Schaid D.J. , Pankratz V.S. , Vierkant R.A. , Fredericksen Z.S. , Wu Y. , Couch F.J. , et al. .
Source: Breast cancer research and treatment, 2007 Apr; 102(2), p. 237-47.
EPub date: 2006-09-27.
PMID: 17004113
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A comprehensive examination of CYP19 variation and breast density.
Authors: Olson J.E. , Ma C.X. , Pelleymounter L.L. , Schaid D.J. , Pankratz V.S. , Vierkant R.A. , Fredericksen Z.S. , Ingle J.N. , Wu Y. , Couch F. , 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. 623-5.
PMID: 17372263
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A common coding variant in CASP8 is associated with breast cancer risk.
Authors: Cox A. , Dunning A.M. , Garcia-Closas M. , Balasubramanian S. , Reed M.W. , Pooley K.A. , Scollen S. , Baynes C. , Ponder B.A. , Chanock S. , et al. .
Source: Nature genetics, 2007 Mar; 39(3), p. 352-8.
EPub date: 2007-02-11.
PMID: 17293864
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Methylenetetrahydrofolate reductase haplotype tag single-nucleotide polymorphisms and risk of breast cancer.
Authors: Martin Y.N. , Olson J.E. , Ingle J.N. , Vierkant R.A. , Fredericksen Z.S. , Pankratz V.S. , Wu Y. , Schaid D.J. , Sellers T.A. , Weinshilboum R.M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Nov; 15(11), p. 2322-4.
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No association between 25-hydroxyvitamin D and mammographic density.
Authors: Knight J.A. , Vachon C.M. , Vierkant R.A. , Vieth R. , Cerhan J.R. , Sellers T.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Oct; 15(10), p. 1988-92.
PMID: 17035410
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Cancer risk assessment at the atomic level.
Authors: Monteiro A.N. , Couch F.J. .
Source: Cancer research, 2006-02-15; 66(4), p. 1897-9.
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Human aromatase: gene resequencing and functional genomics.
Authors: Ma C.X. , Adjei A.A. , Salavaggione O.E. , Coronel J. , Pelleymounter L. , Wang L. , Eckloff B.W. , Schaid D. , Wieben E.D. , Adjei A.A. , et al. .
Source: Cancer research, 2005-12-01; 65(23), p. 11071-82.
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Preventive health behaviors and familial breast cancer.
Authors: Madlensky L. , Vierkant R.A. , Vachon C.M. , Pankratz V.S. , Cerhan J.R. , Vadaparampil S.T. , Sellers T.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 Oct; 14(10), p. 2340-5.
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Prenatal and perinatal correlates of adult mammographic breast density.
Authors: Cerhan J.R. , Sellers T.A. , Janney C.A. , Pankratz V.S. , Brandt K.R. , Vachon C.M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 Jun; 14(6), p. 1502-8.
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Random-effects Cox proportional hazards model: general variance components methods for time-to-event data.
Authors: Pankratz V.S. , de Andrade M. , Therneau T.M. .
Source: Genetic epidemiology, 2005 Feb; 28(2), p. 97-109.
PMID: 15532036
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Functional evaluation and cancer risk assessment of BRCA2 unclassified variants.
Authors: Wu K. , Hinson S.R. , Ohashi A. , Farrugia D. , Wendt P. , Tavtigian S.V. , Deffenbaugh A. , Goldgar D. , Couch F.J. .
Source: Cancer research, 2005-01-15; 65(2), p. 417-26.
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Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2.
Authors: Goldgar D.E. , Easton D.F. , Deffenbaugh A.M. , Monteiro A.N. , Tavtigian S.V. , Couch F.J. , Breast Cancer Information Core (BIC) Steering Committee .
Source: American journal of human genetics, 2004 Oct; 75(4), p. 535-44.
EPub date: 2004-08-02.
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Genetic epidemiology of BRCA1.
Authors: Couch F.J. .
Source: Cancer biology & therapy, 2004 Jun; 3(6), p. 509-14.
EPub date: 2004-06-24.
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Interaction of adolescent anthropometric characteristics and family history on breast cancer risk in a Historical Cohort Study of 426 families (USA).
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Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes.
Authors: Shield A.J. , Thomae B.A. , Eckloff B.W. , Wieben E.D. , Weinshilboum R.M. .
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Bilateral oophorectomy and breast cancer risk reduction among women with a family history.
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Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics.
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Source: British journal of pharmacology, 2003 Aug; 139(8), p. 1373-82.
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TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors.
Authors: Sinclair C.S. , Adem C. , Naderi A. , Soderberg C.L. , Johnson M. , Wu K. , Wadum L. , Couch V.L. , Sellers T.A. , Schaid D. , et al. .
Source: Cancer research, 2002-07-01; 62(13), p. 3587-91.
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Association of correlates of endogenous hormonal exposure with breast cancer risk in 426 families (United States).
Authors: Grabrick D.M. , Vierkant R.A. , Anderson K.E. , Cerhan J.R. , Anderson V.E. , Seller T.A. .
Source: Cancer causes & control : CCC, 2002 May; 13(4), p. 333-41.
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Investigation of an interaction of alcohol intake and family history on breast cancer risk in the Minnesota Breast Cancer Family Study.
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Source: Cancer, 2001-07-15; 92(2), p. 240-8.
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Cigarette smoking increases risk for breast cancer in high-risk breast cancer families.
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Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2001 Apr; 10(4), p. 327-32.
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