Associations of erythrocyte ω‐3 fatty acids with biomarkers of ω‐3 fatty acids and inflammation in breast tissue

Roy, Satavisha; Brasky, Theodore M.; Belury, Martha A.; Krishnan, Shiva; Cole, Rachel M.; Marian, Cătălin; Yee, Lisa D.; Llanos, Adana A.M.; Freudenheim, Jo L.; Shields, Peter G.

doi:10.1002/ijc.29675

Cited by 19 publications

(12 citation statements)

References 40 publications

(73 reference statements)

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“…Consistent with this finding, RBC and cardiac/breast tissue EPA content correlate strongly after omega-3 PUFA supplementation in humans [14][15][16], and RBC omega-3 PUFA levels correlate with omega-3 PUFA content in multiple mouse and rat tissues after dietary supplementation [17][18].…”

Section: Discussionsupporting

confidence: 65%

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

Watson

Cockbain

Spencer

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases, Prostaglandins Leukotrienes and Essential Fatty Acids, http://dx.doi.org/10.1016/j.plefa.2016.10.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractWe investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (A.J. Cockbain et al, 2014). There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26 [±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance.

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Section: Discussionsupporting

confidence: 65%

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

Watson

Cockbain

Spencer

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…Red blood cell (RBC) membrane ω-3 PUFA levels (as a validated surrogate biomarker of ω-3 PUFA tissue exposure 84,85 ) have been long established as a biomarker of dietary ω-3 PUFA exposure in cancer epidemiological studies. 86 Between 2014 and 2016, ω-3 PUFA levels were used in RCTs of ω-3 PUFAs as a biomarker of target tissue ω-3 PUFA exposure (termed 'bioavailability' here), but also as a possible indicator of compliance and/or placebo group 'contamination' by over-the-counter (OTC) ω-3 PUFA use.…”

Section: Anticolorectal Cancer Activity Of Eicosapentaenoic Acidmentioning

confidence: 99%

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT

et al. 2019

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Background The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer (CRC) chemoprevention, aligned with an excellent safety profile. Objectives The objectives were to determine whether or not EPA prevents colorectal adenomas, either alone or in combination with aspirin, and to assess the safety/tolerability of EPA, in the free fatty acid (FFA) form or as the triglyceride (TG), and aspirin. Design This was a randomised, blinded, placebo-controlled, 2 × 2 factorial trial. Setting The NHS Bowel Cancer Screening Programme (BCSP). Participants Patients (aged 55–73 years) identified as ‘high risk’ (i.e. those who have five or more colorectal adenomas of < 10 mm in size or three or more colorectal adenomas if one is ≥ 10 mm in size) at screening colonoscopy. Interventions The interventions were capsules containing 2000 mg of 99% EPA–FFA or 2780 mg of 90% EPA–TG (equivalent to 2000 mg of FFA) taken daily, or identical placebo capsules; and 300 mg of aspirin taken daily, or an identical placebo, enteric-coated tablet. Both were taken for ≈1 year until surveillance colonoscopy. All participants and staff were unaware of treatment allocation. Main outcome measures The primary outcome was the number of participants with one or more colorectal adenomas [adenoma detection rate (ADRa)] at surveillance colonoscopy. Outcomes were analysed for all participants with observable follow-up data by an ‘at-the-margins’ approach, adjusted for BCSP site and by the need for repeat baseline endoscopy. Secondary outcome measures – these included the number of colorectal adenomas per patient [mean adenomas per patient (MAP)], ‘advanced’ ADRa and colorectal adenoma location (right/left) and type (conventional/serrated). Results Between November 2011 and June 2016, 709 participants were randomised, with 707 providing data (80% male, mean age 65 years). The four treatment groups (EPA + aspirin, n = 177; EPA, n = 179; aspirin, n = 177; placebo, n = 176) were well matched for baseline characteristics. Tissue EPA levels and tolerability were similar for FFA and TG users. There was no evidence of any difference in ADRa between EPA users (62%) and non-users (61%) [risk difference –0.9%, 95% confidence interval (CI) –8.8% to 6.9%] or for aspirin users (61%) versus non-users (62%) (risk difference –0.6%, 95% CI –8.5% to 7.2%). There was no evidence of an interaction between EPA and aspirin for ADRa. There was no evidence of any effect on advanced ADRa of either EPA (risk difference –0.6%, 95% CI –4.4% to 3.1%) or aspirin (risk difference –0.3%, 95% CI –4.1% to 3.5%). Aspirin use was associated with a reduction in MAP [incidence rate ratio (IRR) 0.78, 95% CI 0.68 to 0.90), with preventative efficacy against conventional (IRR 0.82, 95% CI 0.71 to 0.94), serrated (IRR 0.46, 95% CI 0.25 to 0.87) and right-sided (IRR 0.73, 95% CI 0.61 to 0.88) lesions, but not left-sided (IRR 0.85, 95% CI 0.69 to 1.06) adenomas. There was evidence of chemopreventive efficacy of EPA on conventional (IRR 0.86, 95% CI 0.74 to 0.99) and left-sided (IRR 0.75, 95% CI 0.60 to 0.94) adenomas, but not on total MAP (IRR 0.91, 95% CI 0.79 to 1.05) or serrated (IRR 1.44, 95% CI 0.79 to 2.60) or right-sided (IRR 1.02, 95% CI 0.85 to 1.22) adenomas. EPA and aspirin treatment were well tolerated, with excess mild/moderate gastrointestinal (GI) adverse events (AEs) in the EPA alone group. There were six GI bleeding AEs. Conclusion EPA and aspirin treatment were not associated with a reduction in ADRa. However, both agents displayed evidence of chemopreventive efficacy, based on adenoma number reduction, which was specific to adenoma type and location, and is compatible with known anti-CRC activity of aspirin. Limitations Limitations of the trial included the failure to recruit to the target sample size of 853, and an unexpected switch of EPA formulation mid-trial. Future work A future objective should be to understand the mechanism(s) of action of EPA and aspirin using the trial biobank. Established trial infrastructure will enable future trials in the BCSP. Trial registration Current Controlled Trials ISRCTN05926847. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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“…As obesity progresses, blood adiponectin falls and clinical insulin resistance develops with increasing fatty acid storage in liver and muscle (1). Systemic increases in IL6 result in liver production of CRP and systemic rises in this cytokine (2). Low blood adiponectin or adiponectin:leptin ratio, and higher systemic levels of CRP and estrogen, have generally been found to be associated with postmenopausal breast cancer (3).…”

Section: ó2018 Aacrmentioning

confidence: 99%

The Conundrum of Omega-3 Fatty Acids in Cancer Prevention Studies: Which One? How Much? What Biomarkers?

Fabian

Kimler

2018

Cancer Prevention Research

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Marine omega-3 fatty acids promote resolution of inflammation and have potential to reduce risk of obesity-related breast cancer. For prevention trials in obese women, inflammatory cytokines, aromatase, and measures of breast immune cell infiltration are logical, as are biomarkers of growth factor, adipokine, and estrogen signaling. Where best to look for marker change: in the circulation (easiest), in benign breast tissue (most relevant), or in visceral adipose (inflammation often most marked)? A null biomarker modulation trial may reflect limitations in design, source and dose of fatty acids, or biomarkers and should not lead to premature abandonment of marine omega-3 fatty acids for cancer prevention. .

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Associations of erythrocyte ω‐3 fatty acids with biomarkers of ω‐3 fatty acids and inflammation in breast tissue

Cited by 19 publications

References 40 publications

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT

The Conundrum of Omega-3 Fatty Acids in Cancer Prevention Studies: Which One? How Much? What Biomarkers?

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