In Utero Exposure and Breast Cancer Development: an Epigenetic Perspective

Abstract

The ubiquitous and detrimental disease of breast cancer requires continual research into new and alternative forms of treatment and prevention. The emerging field of epigenetics is beginning to unfold an array of contemporary approaches to reduce the risk and improve the clinical approach to breast cancer. The information contained in this non-systematic review highlights and expands on the estrogen-based model of breast cancer epigenetics to provide an overview of epigenetic alterations induced by nutrition and environmental exposure. The majority of evidence suggests that various sources of excess estrogen correlate to future breast cancer development. In addition, maternal macro- and micronutrient balance appear to play a role in genomic regulation, and preliminary data suggest that specific superfoods, such as blueberries, have a protective epigenetic effect. Identifying the influence of environmental toxicants, hormonal exposure, maternal nutrition, and maternal disease on fetal epigenetics may have potential for development of new therapeutic approaches for the prevention of breast cancer.

Developmental origins of health and disease

“…Animal studies also show causal relationships between developmental chemical exposures and diseases that have not been examined in human studies due to the long lag time between exposures and disease onset such as breast and prostate cancer, neurodegenerative diseases, cardiovascular diseases and reproductive conditions including endometriosis, and uterine fibroids 13-15 .…”

Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer

“…Dysregulation or aberrant deposition of histone acetylation is a common trait of several malignant tumors and has been a successful target for therapeutic intervention (66,67). Many of the histone residues that are methylated (e.g., H3K4, H3K9, and H3K27) can alternatively be modified by acetylation, generally promoting gene activation and antagonizing gene repression (68)(69)(70)(71)(72)(73)(74). Specifically, H3K4 acetylation may play a role in establishing or maintaining bivalent domains in certain cell types.…”

“…While estradiol has biological roles in both normal proliferation and normal differentiation, providing the cellular plasticity needed for tissue remodeling throughout the reproductive years, unregulated estradiol exposure can result in constitutive activation of metabolic and cell cycle regulatory genes and increases the risk of breast cancer. There is strong clinical and epidemiological data linking estrogen exposure with an increased risk of developing breast cancer (68)(69)(70)(71)(72)(73)(74).…”