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- Title
Genomic signature of parity in the breast of premenopausal women.
- Authors
Santucci-Pereira, Julia; Zeleniuch-Jacquotte, Anne; Afanasyeva, Yelena; Zhong, Hua; Slifker, Michael; Peri, Suraj; Ross, Eric A.; López de Cicco, Ricardo; Zhai, Yubo; Nguyen, Theresa; Sheriff, Fathima; Russo, Irma H.; Su, Yanrong; Arslan, Alan A.; Bordas, Pal; Lenner, Per; Åhman, Janet; Landström Eriksson, Anna Stina; Johansson, Robert; Hallmans, Göran
- Abstract
<bold>Background: </bold>Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women.<bold>Methods: </bold>Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues.<bold>Results: </bold>Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues.<bold>Conclusions: </bold>Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.
- Subjects
GENE expression profiling; BREAST; BREAST biopsy; GENE expression; GENOMIC imprinting
- Publication
Breast Cancer Research, 2019, Vol 21, Issue 1, pN.PAG
- ISSN
1465-5411
- Publication type
journal article
- DOI
10.1186/s13058-019-1128-x