Abstract

Introduction The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations. Methods BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry. Results 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients (P < 0.00001) and in controls (P < 0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation (P = 0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A (P = 0.02). Conclusions DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.

Highlights

  • The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes

  • At T1, we found an increase in 19,20-Epoxydocosapentaenoic acids (EDPs) levels in breast cancer (BC) patients (P < 0 00001) and in controls (P < 0 001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation (P = 0 03)

  • Luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A (P = 0 02)

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Summary

Introduction

The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population. Metabolites of DHA, named as epoxydocosapentaenoic acids (EDPs), deriving from the conversion of DHA by cytochrome P450 epoxygenases, are suggested to be responsible for some of the beneficial effects attributed to omega-3 PUFAs and omega-3-rich foods, such as fish oil, and to mediate some of the health-promoting effects of DHA [5]. Evidences showed that omega-3 fatty acid metabolites and mainly EDPs mediate several beneficial effects in chronic conditions, including chronic pain and angiotensin II-dependent hypertension, by anti-inflammatory properties, and in kidney disease [6,7,8,9,10].

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