Grants and Fellowships | 2014

47 Post-Doctoral Fellowships Breast Cancer and Epigenetics One plausible mechanism by which the environment can alter breast cancer susceptibility is through epigenetic effects on somatic cells, leading to activation or silencing of key genes in critical pathways. Epigenetic processes which include DNA methylation, altered packaging with histones and genomic imprinting and aberrations of these processes play a role in causing cancer. Accumulating data suggest not only that global DNA hypomethylation may be related to cancer but that environmental factors may alter DNA methylation patterns. In addition, there is evidence that environmental exposures associated with cancer risk are also associated with genomic DNA hypomethylation. While epigenetic modifications may occur at any age, they are more likely to occur early in embryonic or fetal development, during puberty, and in old age. We are conducting a unique study on human exposure to organchlorines during pregnancy and the effect that these compounds may have on epigenetic events during two windows of exposure that are critical to the breast: (1) pregnancy, when ductal proliferation places the breast at risk for carcinogenesis in the mother and (2) the prenatal period when breast cellular differentiation places the breast at risk for carcinogenesis in the daughter. There are few human studies where exposure to endocrine active compounds during these critical periods can be measured directly in relation to subsequent breast cancer risk. The proposed research is a novel and unique opportunity to address this gap by efficiently using an existing cohort that spans two generations. This study uses a 50-year follow-up of the Child Health and Development Studies (CHDS) Pregnancy Cohort. The cohort includes maternal pregnancy serum samples that were collected during peak exposure to organochlorine pesticides and polychlorinated biphenyls in the 1960’s, prior to the ban on these chemicals. DNA methylation in adulthood will be added as an outcome to the study of in utero organochlorine exposure and breast density (n=200). In addition we will examine whether prenatal organochlorine exposure is associated with DNA methylation measured using the adult sera of women. A review article published as part of this study examined the differences in white blood cells DNA methylation by selected risk factors. The conclusions uniquely suggest that there are correlations between early life exposure to environmental factors and DNA methylation. Research publications (1) Terry, M.B., Delgado-Cruzata, L., Vin-Raviv, N., Wu, H.C., & Santella, R.M. (2011). DNA methylation in white blood cells: Association with risk factors in epidemiologic studies. Epigenetics, 6 (7), 1-10. (2) Delgado-Cruzata, L., Vin-Raviv, N., Tehranifar, P., Flom, J., Reynolds, D., Gonzalez, K., Santella, R.M., & Terry, M.B. (2014). Correlations in global DNA methylation measures in peripheral blood mononuclear cells and granulocytes. Accepted, Epigenetics , 2014. Fellow Neomi Vin-Raviv Columbia University, USA Supervisor Mary Beth Terry 2011-2013