Breast Cancer: Mechanisms Involved in Action of Phytoestrogens and Epigenetic Changes

In this review, we consider phytoestrogens and different epigenetic modifications in breast cancer. Epigenetic phenomena are mediated by several molecular mechanisms comprising histone modifications, small non- coding or anti-sense RNA and DNA methylation. These different modifications are closely interrelated. De-regulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in breast carcinogenesis. The incidence and mortality rates of breast cancer are high in the Western world compared with countries in Asia. There are also differences in the breast cancer incidence rates in different Western countries. This could be related to phytoestrogens. Breast cancer remains the first cause of cancer-related mortality in women. This can be explained by the high histological and molecular heterogeneity of the disease, making it hard to choose a therapy adapted to each patient. Over this past year, several groups have evaluated the epigenetic component of breast cancer, as epigenetics appears to be important in carcinogenesis. The progression through the multiple steps of breast cancer from epithelial hypertrophy to highly invasive breast carcinoma involves multiple coordinated changes in gene expression programming. Such coordinated changes are bound to be controlled by global mechanisms of gene expression programming. The genome is programmed by the epigenome, which consists of the chromatin structure, a pattern of modification of DNA by DNA methylation, and a profile of expression of non-coding RNAs, such as microRNA. The revolution of epigenetics has re-vitalized cancer research, shifting focus away from somatic mutation towards a more global perspective involving the dynamic states of chromatin. Disruption of chromatin organization can directly and indirectly precipitate genomic instability and transformation. Epigenetic changes are reversible and may lead to loss or gain of biological functions. More importantly, many of the elucidated epigenetic changes are linked to pathogenesis of human diseases, including cancer. Epigenetic aberrations arise early in carcinogenesis, before gene mutations in DNA supplies targets for early detection. The incidence and mortality rates of breast cancer are high in the Western world compared with countries in Asia. There are also differences in regional cancer incidence rates in the Western countries. Several studies involving immigrants to Western countries suggest that lifestyle and diet are two of the main causes of these differences. In Eastern countries, the incidence of breast cancer is approximately one-third compared to that of Western countries, whilst the high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have estrogenic effects. Phytoestrogens