Nicole Miller

Introduction. Epigenetic changes, including hypomethylation of global DNA, hypermethylation of tumor suppressor gene promoters, and abnormal histone modifications, have been determined genetic hallmarks of cancer². Since the 1970s, dietary fat has been studied in association with epigenetic disruptions causing breast cancer³. Studies in both humans and rat models note the mammary gland to be most sensitive to the environment and dietary influences during puberty⁴. The results of previous studies, however, show inconsistencies due to differences in study design, measurement error, and difficulty interpreting findings^1,3,4. In order to determine the efficacy of intervention with nutritional components for breast cancer prevention, the interrelationship between dietary lipids, epigenetic modifications, and breast cancer must be better understood². Methods. The rat dimethylbenz(a)anthracene (DBMA)-induced breast cancer model was used. Rats were fed one of three diets from weaning or induction with DMBA: low-fat, high corn oil, or high extra-virgin olive oil. Global and gene specific (RASSF1A, TIMP3) DNA methylation in mammary glands and tumors was analyzed using LUMA and bisulfite pyrosequencing assays.  Real time PCR was also used to measure mRNA levels to determine the expression of RASSF1A and TIMP3 in mammary glands and tumors². Results. In analyzing global DNA methylation, variations were found along time, specifically finding decreases in methylation at puberty. In addition, rats fed the high-olive oil diet had the highest levels of global DNA methylation at all ages in comparison to rats fed other diets. Analysis of gene specific DNA promoter methylation showed an increase in methylation of RASSF1A and TIMP3 tumor suppressor genes in rats fed a high corn oil diet. The expression of TIMP3 was notably shown to decrease over time in rats fed high fat diets, especially corn oil, when compared with rats fed a low-fat diet. At the end of puberty, however, there was a reported increase in expression of both tumor suppressor genes in mammary glands, possibly due to the proliferation and differentiation associated with mammary gland development². Conclusion. Studies have shown that dietary fat may influence epigenetic modifications associated with breast cancer, especially during puberty⁴. Specifically, olive oil may have a protective effect by inhibiting global DNA hypomethylation, while corn oil and high-fat diets may have harmful effects by stimulating methylation and consequently decreased expression of tumor suppressor genes (RASSF1A and TIMP3). Individuals may be most susceptible to the effects of different dietary lipids during puberty, when tumor suppressor gene expression is enhanced and global DNA is hypomethylated. The timing and make—up of nutritional interventions may therefore be determined based on this data.

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2. Rodríguez-Miguel C, Moral R, Escrich R, Vela E, Solanas M, Escrich E. The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model. Coleman WB, ed. PLoS ONE. 2015;10(9):e0138980. doi:10.1371/journal.pone.0138980.
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