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Genes 2017, 8(5), 144;

DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated with Survival Outcomes in Breast Cancer Patients

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA
Fox Chase Cancer Center, Temple University Health System, 333 Cottman Ave, Philadelphia, PA 19111, USA
Department of Pharmacology and Toxicology University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA
Authors to whom correspondence should be addressed.
Academic Editor: Montserrat Corominas
Received: 10 March 2017 / Revised: 25 April 2017 / Accepted: 9 May 2017 / Published: 15 May 2017
(This article belongs to the Special Issue Integrative Genomics and Systems Medicine in Cancer)
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Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been reported to predispose for and against mammary cancer, respectively, in adult rats. Since the changes in cancer susceptibility occurs in the absence of the original chemical exposure, we have investigated the potential of epigenetics to account for these changes. DNA methylation studies reveal that prepubertal BPA exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal exposure to GEN and BPA + GEN revealed pathways involved in maintenance of cellular function, indicating that the presence of GEN either reduces or counters some of the alterations caused by the carcinogenic properties of BPA. We subsequently evaluated the potential of epigenetic changes in the rat mammary tissues to predict survival in breast cancer patients via the Cancer Genomic Atlas (TCGA). We identified 12 genes that showed strong predictive values for long-term survival in estrogen receptor positive patients. Importantly, two genes associated with improved long term survival, HPSE and RPS9, were identified to be hypomethylated in mammary glands of rats exposed prepuberally to GEN or to GEN + BPA respectively, reinforcing the suggested cancer suppressive properties of GEN. View Full-Text
Keywords: DNA-methylation; Bisphenol A; genistein DNA-methylation; Bisphenol A; genistein

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Jadhav, R.R.; Santucci-Pereira, J.; Wang, Y.V.; Liu, J.; Nguyen, T.D.; Wang, J.; Jenkins, S.; Russo, J.; Huang, T.H.-M.; Jin, V.X.; Lamartiniere, C.A. DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated with Survival Outcomes in Breast Cancer Patients. Genes 2017, 8, 144.

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