Omega-3 polyunsaturated fatty acids: moving towards precision use for prevention and treatment of colorectal cancer.

Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs.

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

We 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 (Cockbain et al., 2014) [8]. 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. There was little evidence of 'contamination' in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16-0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients.