Dietary fat and obesity as modulators of breast cancer risk: Focus on DNA methylation

Abstract

Breast cancer (BC) is the most common cancer and second leading cause of cancer mortality in women worldwide. Validated biomarkers enhance efforts for early detection and treatment, which reduce the risk of mortality. Epigenetic signatures have been suggested as good biomarkers for early detection, prognosis and targeted therapy of BC. Here, we highlight studies documenting the modifying effects of dietary fatty acids and obesity on BC biomarkers associated with DNA methylation. We focus our analysis on changes elicited in writers of DNA methylation (i.e., DNA methyltransferases), global DNA methylation and gene‐specific DNA methylation. To provide context, we precede this discussion with a review of the available evidence for an association between BC incidence and both dietary fat consumption and obesity. We also include a review of well‐vetted BC biomarkers related to cytosine‐guanine dinucleotides methylation and how they influence BC risk, prognosis, tumour characteristics and response to treatment. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

“…This study demonstrated that changes in dietary habits and other lifestyle factors were associated with DNA methylation changes [100]. In summary, DNA methylation biomarkers should be useful to monitor lifestyle interventions, and differentially methylated sites obesity-associated could serve as targets for BC prevention [101].…”

ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

“…In this context, it was demonstrated that the methylation levels of ZNF577 were also observed in association with adiposity and menopausal status, and the direction of differences in methylation levels were inverse to that in expression of this gene in the blood leukocytes. Dietary habits are also a risk factor for developing cancer and obesity, as well as both factors were related to the regulation of the methylation profile (44)(45)(46). Thus, when the methylation levels of ZNF577 were evaluated according to the dietary habits, breast cancer patients who adhered to a Mediterranean diet and who specifically consumed higher amounts of vegetables, legumes, and fish showed the highest levels of methylation in ZNF577, independently of menopausal and obesity status.…”

Highlights into the pharmacology of nutraceuticals

“…Schwingshackl et al () introduce the field of nutrigenomics in relation to the Mediterranean diet, whereby nutritional agents can affect the genome of the host through a variety of mechanisms, including epigenetics and generation of long non‐coding RNAs. The topic is reinforced in other two review articles of this themed issue (Beetch et al, ; Donovan et al, ). Epigenetic changes wrought by environmental exposure and inflammation may underpin the global burden of chronic disease.…”

“…Enough safety data have been collated to allow hydroxytyrosol to gain novel food status by EFSA. The effects of EVOO to modify the methylome in breast cancers is also explored by Donovan, Wren, Cenker, Selmin and Romagnolo (). The theme of polyphenols is continued by Man et al () in the context of the microbiota where the metagenomic effects of nutraceuticals are an emerging field.…”