Extra virgin olive oil and corn oil and epigenetic patterns in breast cancer

Abstract

Breast cancer is the leading neoplasia in women worldwide. Nutrition and especially dietary lipids can influence mammary carcinogenesis through multiple mechanisms. This works aims to get insight into the effects of two common oils, extra virgin olive oil (EVOO) and corn oil, on mammary carcinogenesis and the molecular mechanisms of such effects. The administration of a diet high in corn oil (HCO) from weaning had a clear stimulating effect on 7,12-dimethylbenz(a) anthracene-induced mammary carcinogenesis, increasing the morphological and clinical degree of tumor malignancy, while a high-EVOO diet has a weak tumor-enhancing effect. The HCO diet modified gene expression profiles in mammary gland and tumors, downregulating genes with a role in apoptosis and immune system. On the contrary, the high-EVOO diet mainly modulated genes with a role in metabolism. These effects may be a consequence of an influence on the epigenetic machinery. Thus, the high-EVOO diet increased global DNA methylation in the mammary gland, mainly around puberty, and also in experimental mammary tumors. In relation to gene-specific methylation, the HCO diet, but not the high EVOO one, increased the total DNA methyltransferase activity in mammary glands and tumors, concomitantly with the increase in Rassf1a and Timp3 promoter methylation. Both high-fat diets may influence the modification of histones (the levels of H3K4me2, H3K27me3, H4K16ac, and H4K20me3), especially in the mammary gland. Although there is little data reported at other epigenetic levels, the differential effects of the diets are likely to be also due to different modification of microRNA patterns. Considering the unspecific tumor-promoting effect of all high-fat diets, the results suggest some beneficial effect of EVOO that counteracts the deleterious influence of excessive fat intake. The EVOO minor components may have a key role in such beneficial effects modulating, at least in part, the epigenetic machinery.