Grant Number:	5R01CA093599-02 Interpret this number
Primary Investigator:	Russo, Jose
Organization:	Fox Chase Cancer Center
Project Title:	Genomic Basis of Reproductive History on Breast Cancer
Fiscal Year:	2003

DESCRIPTION (provided by applicant): Although the agents and the mechanisms that cause breast cancer are still uncertain, there is substantial evidence that breast cancer risk is strongly dependent on endocrinological and reproductive conditions, such as early menarche, late menopause, and nulliparity. An early first full term pregnancy, on he other hand, confers a lifetime protection. Experimentally we have demonstrated that the protection conferred by pregnancy is mediated by induction of breast differentiation, which is manifested through obular development, reduced cell proliferation and steroid hormone receptor content, and a "genomic signature" that is associated with refractoriness to chemically induced carcinogenesis. This application proposes to test the hypothesis that early pregnancy imprints in the breast permanent genomic changes that reduce the lifetime risk of the developing breast cancer. This hypothesis will be demonstrated through the following specific aims: 1: To characterize the specific gene expression profile of women at "low" and 'high" risk of developing breast cancer because of reproductive history. Gene expression in normal breast tissue obtained from postmenopausal women with a history of one or more early full term pregnancies will he compared to gene expression in normal breast tissue from postmenopausal women who are nulliparous. For this purpose we will perform a large-scale analysis of gene expression using available human cDNA libraries for determining the expression pattern of known and unknown (ESTs) genes. 2: To determine if gene clusters differentially expressed in women at risk of developing breast cancer because of reproductive history (identified in Specific aim 1) are differentially expressed in the breast issue of postmenopausal women with breast cancer compared to postmenopausal women who do not have breast cancer. For this purpose we will perform a case-control study to compare gene expression profiles in the normal, breast tissue of postmenopausal women with invasive breast cancer vs. postmenopausal women with benign breast disease. Knowledge gained through these studies will allow us to identify the "genomic signature" induced by an early pregnancy, and that if proven to be functionally relevant would serve as molecular markers for assessing breast cancer risk in large populations.




Mimicking Pregnancy As A Strategy For Breast Cancer Prevention
Authors: Santucci-Pereira J. , George C. , Armiss D. , Russo I.H. , Vanegas J.E. , Sheriff F. , de Cicco R.L. , Su Y. , Russo P.A. , Bidinotto L.T. , et al. .
Source: Breast Cancer Management, 2013-07-01 00:00:00.0; 2(4), p. 283-294.
PMID: 24738009
Related Citations

Cancer Behavior: An Optimal Control Approach
Authors: Gutiérrez P.J. , Russo I.H. , Russo J. .
Source: International Journal Of Immunological Studies, 2009; 1(1), p. 31-65.
PMID: 22247736
Related Citations

Full-term Pregnancy Induces A Specific Genomic Signature In The Human Breast
Authors: Russo,J. , Balogh,G.A. , Russo,I.H. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2008 Jan; 17(1), p. 51-66.
PMID: 18199711
Related Citations

The Breast Of Parous Women Without Cancer Has A Different Genomic Profile Compared To Those With Cancer
Authors: Balogh,G.A. , Russo,J. , Mailo,D.A. , Heulings,R. , Russo,P.A. , Morrison,P. , Sheriff,F. , Russo,I.H. .
Source: International Journal Of Oncology, 2007 Nov; 31(5), p. 1165-75.
PMID: 17912444
Related Citations

Methodological Approach To Study The Genomic Profile Of The Human Breast
Authors: Balogh,G.A. , Heulings,R. , Mailo,D. , Wang,R. , Li,Y.S. , Hardy,R. , Russo,J. .
Source: International Journal Of Oncology, 2007 Aug; 31(2), p. 253-60.
PMID: 17611680
Related Citations

Immune-surveillance And Programmed Cell Death-related Genes Are Significantly Overexpressed In The Normal Breast Epithelium Of Postmenopausal Parous Women
Authors: Balogh,G.A. , Russo,I.H. , Spittle,C. , Heulings,R. , Russo,J. .
Source: International Journal Of Oncology, 2007 Aug; 31(2), p. 303-12.
PMID: 17611686
Related Citations

The Genomic Signature Of Breast Cancer Prevention
Authors: Russo,J. , Balogh,G. , Mailo,D. , Russo,P.A. , Heulings,R. , Russo,I.H. .
Source: Recent Results In Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer, 2007; 174, p. 131-50.
PMID: 17302192
Related Citations

Molecular Basis Of Pregnancy-induced Breast Cancer Protection
Authors: Russo,J. , Balogh,G.A. , Heulings,R. , Mailo,D.A. , Moral,R. , Russo,P.A. , Sheriff,F. , Vanegas,J. , Russo,I.H. .
Source: European Journal Of Cancer Prevention : The Official Journal Of The European Cancer Prevention Organisation (ecp), 2006 Aug; 15(4), p. 306-42.
PMID: 16835503
Related Citations

Genomic Signature Induced By Pregnancy In The Human Breast
Authors: Balogh,G.A. , Heulings,R. , Mailo,D.A. , Russo,P.A. , Sheriff,F. , Russo,I.H. , Moral,R. , Russo,J. .
Source: International Journal Of Oncology, 2006 Feb; 28(2), p. 399-410.
PMID: 16391795
Related Citations

The Concept Of Stem Cell In The Mammary Gland And Its Implication In Morphogenesis, Cancer And Prevention
Authors: Russo,J. , Balogh,G.A. , Chen,J. , Fernandez,S.V. , Fernbaugh,R. , Heulings,R. , Mailo,D.A. , Moral,R. , Russo,P.A. , Sheriff,F. , et al. .
Source: Frontiers In Bioscience : A Journal And Virtual Library, 2006; 11, p. 151-72.
PMID: 16146722
Related Citations

Breast Differentiation And Its Implication In Cancer Prevention
Authors: Russo,J. , Mailo,D. , Hu,Y.F. , Balogh,G. , Sheriff,F. , Russo,I.H. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2005-01-15 00:00:00.0; 11(2 Pt 2), p. 931s-6s.
PMID: 15701889
Related Citations

The Protective Role Of Pregnancy In Breast Cancer
Authors: Russo,J. , Moral,R. , Balogh,G.A. , Mailo,D. , Russo,I.H. .
Source: Breast Cancer Research : Bcr, 2005; 7(3), p. 131-42.
PMID: 15987443
Related Citations

Difference In Gene Expression Profile In Breast Epithelial Cells From Women With Different Reproductive History
Authors: Guo S. , Russo I.H. , Russo J. .
Source: International Journal Of Oncology, 2003 Oct; 23(4), p. 933-41.
PMID: 12963971
Related Citations