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Belitskaya-Levy I , Zeleniuch-Jacquotte A , Russo J , Russo IH , Bordas P , Ahman J , Afanasyeva Y , Johansson R , Lenner P , Li XC , de Cicco RL , Peri S , Ross E , Russo PA , Santucci-Pereira J , Sheriff FS , Slifker M , Hallmans G , Toniolo P , Arslan AA
Characterization of a Genomic Signature of Pregnancy Identified in the Breast
Cancer Prevention Research. 2011 Sep;4(9) :1457-1464
PMID: WOS:000294490100017   
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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. Cancer Prev Res; 4(9); 1457-64. (C) 2011 AACR.
Notes
Belitskaya-Levy, Ilana Zeleniuch-Jacquotte, Anne Russo, Jose Russo, Irma H. Bordas, Pal Ahman, Janet Afanasyeva, Yelena Johansson, Robert Lenner, Per Li, Xiaochun de Cicco, Ricardo Lopez Peri, Suraj Ross, Eric Russo, Patricia A. Santucci-Pereira, Julia Sheriff, Fathima S. Slifker, Michael Hallmans, Goran Toniolo, Paolo Arslan, Alan A. Avon Foundation for Women[02-2008-034] This work was supported by grant 02-2008-034 from the Avon Foundation for Women Breast Cancer Research Program. 29 Amer assoc cancer research Philadelphia 814xi