Abstract 2360: Gene expression profile induced by pregnancy in the breast of premenopausal women

Abstract

Abstract We previously reported that having completed a full term pregnancy (FTP) confers specific gene expression patterns in the breast of healthy postmenopausal women [Belitskaya-Levy, I. et al. 2011, Peri, S. et al. 2012 and Russo, J. 2012]. In the present work, we report on gene expression differences in the breast of parous versus nulliparous healthy premenopausal women. Using Affymetrix Human Genome U133 Plus 2.0 microarrays, we analyzed the gene expression profile of breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers between the ages of 30 and 47 years who were free of breast pathology. Because of the known short-term increase in breast cancer risk preceding the long-term protective effect of FTP, we also examined gene expression differences in P vs. NP women as a function of time since last FTP. Through multiple regression analysis, controlling for confounders, we found 416 probesets differentially expressed (fold-change ≥ 1.2 and false discovery rate < 10%) comparing all P vs. all NP, and/or, P women whose last FTP was less than 5 years before biopsy vs. all NP women. Among these, 352 probesets, representing 238 genes, were up-regulated, while 64 probesets, representing 48 genes, were down-regulated in parous compared to nulliparous breast. Of interest is that among the up-regulated genes, we observed three expression patterns: 1) transient: genes up-regulated after FTP but whose expression levels rapidly returned to nulliparous levels. These genes were mainly related to immune response (CCL5, CD48, IL7R); 2) long-term changing: genes up-regulated following FTP, whose expression levels decreased with increasing time since last FTP but did not return to nulliparous levels. These genes included genes related to immune response (CD38, CXCL10) and development (DKK3, LAMA2); 3) long-term constant: genes that remained up-regulated in parous compared to nulliparous breast, independent of time since last FTP. These genes were mainly involved in developmental processes (BHLHE22, FZD8, KRT5), cell differentiation (RASGRP1, DSC3) and chromatin remodeling (NAP1L2). This study shows that a FTP induces long-term expression changes in genes related to the processes of development, cell differentiation and chromatin remodeling as we also found in the parous postmenopausal breast. Additionally, the transiently activated genes related to immune response during the first five years after FTP may play a role in the short-term increase of breast cancer risk following FTP. A better understanding of the molecular effects of parity on the breast may help the development of novel strategies for preventing breast cancer. (This work was supported by Avon Foundation for Women Breast Cancer Research Program grant 02-2010-117 and by NIH core grant CA06927 to Fox Chase Cancer Center). Citation Format: Julia Santucci-Pereira, Anne Zeleniuch-Jacquotte, Yelena Afanasyeva, Hua Zhong, Eric A. Ross, Michael Slifker, Suraj Peri, Ricardo López de Cicco, Yubo Zhai, Irma H. Russo, Theresa Nguyen, Fathima Sheriff, Alan A. Arslan, Pal Bordas, Per Lenner, Janet Åhman, Anna-Stina L. Eriksson, Robert Johansson, Göran Hallmans, Paolo Toniolo, Jose Russo. Gene expression profile induced by pregnancy in the breast of premenopausal women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2360. doi:10.1158/1538-7445.AM2014-2360