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.