title: Characterization of a genomic signature of pregnancy identified in the breast.
abstract: The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.
authors.affiliation: Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Belitskaya-Lévy
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.forename: Jose
authors.initials: J
authors.lastname: Russo
authors.forename: Irma H
authors.initials: IH
authors.lastname: Russo
authors.forename: Pal
authors.initials: P
authors.lastname: Bordás
authors.forename: Janet
authors.initials: J
authors.lastname: Ahman
authors.forename: Yelena
authors.initials: Y
authors.lastname: Afanasyeva
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.forename: Per
authors.initials: P
authors.lastname: Lenner
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.forename: Ricardo López
authors.initials: RL
authors.lastname: de Cicco
authors.forename: Suraj
authors.initials: S
authors.lastname: Peri
authors.forename: Eric
authors.initials: E
authors.lastname: Ross
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Russo
authors.forename: Julia
authors.initials: J
authors.lastname: Santucci-Pereira
authors.forename: Fathima S
authors.initials: FS
authors.lastname: Sheriff
authors.forename: Michael
authors.initials: M
authors.lastname: Slifker
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Paolo
authors.initials: P
authors.lastname: Toniolo
authors.forename: Alan A
authors.initials: AA
authors.lastname: Arslan
mesh_terms: D000328:Adult; D000368:Aged; D002448:Cell Adhesion; D002453:Cell Cycle; D005260:Female; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010298:Parity; D017698:Postmenopause; D011247:Pregnancy; D015203:Reproducibility of Results