Hypermethylation of the miR-9-3 coding gene in DES-treated breast epithelial cells
2011 Study Abstract
Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs.
Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes.
Diethylstilbestrol (DES) is a synthetic oestrogen that was used to prevent miscarriages in pregnant women between the 1940s and the 1960s. A moderate increase in breast cancer risk has been shown both in daughters of women who were treated with DES during pregnancy, as well as in their daughters. Hsu et al. have demonstrated that the expression of 82 miRNAs (9.1% of the 898 miRNAs evaluated) were altered in breast epithelial cells when exposed to DES. In particular, the suppression of miR-9-3 expression was accompanied by promoter hypermethylation of the miR-9-3 coding gene in DES-treated epithelial cells.
Sources and more information
- Environmental chemical exposures and human epigenetics, International Journal of Epidemiology, Oxford Academic doi.org/10.1093/ije/dyr154, 13 December 2011.
- Epigenetics featured image credit missouri.edu.