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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