Approved Research

Omega-3 polyunsaturated fatty acid intake and colorectal cancer outcomes

Lay summary

Aims: Bowel cancer is the second most common cause of cancer death in the UK. Approximately 50% of bowel cancer could be prevented through lifestyle modifications. We will test whether high dietary intake (fish intake and fish oil supplement use) reflects body levels of omega-3 fatty acids (O3FA) and if they are associated with a lower risk of bowel cancer in UK Biobank (UKBB) participants.

Scientific Rationale: O3FAs are present naturally in oily-fish and prevent bowel cancer in the laboratory. However, evidence that dietary O3FAs reduce bowel cancer risk in people is inconclusive. This is perhaps due to poor recording of the diet and fish oil supplement use. Some studies have tried to confirm dietary O3FA intake by measuring body levels of O3FA but only included a small proportion of participants, making it difficult to draw definite conclusions. More recent results from population-based studies suggests that O3FAs may reduce bowel cancer in certain parts of the bowel (right-side), but were limited by the number of cases and ability to measure O3FA intake accurately. With the forthcoming cancer registry update and O3FA measurements (in 120,000 participants), this study will help answer these important questions.

Project duration: The project will take place over 12 months. We will examine all UKBB participants' O3FA intake through food frequency (fish intake) and medication (fish oil supplement use) questionnaires. We will identify participants who have been diagnosed and/or died with/from bowel cancer. We will specifically look at bowel cancer in different parts of the bowel, which might be affected differently. Using UKBB data that measured body O3FA levels when participants joined the UKBB study, we will investigate whether O3FA intake is linked to body O3FA levels and how this relates to bowel cancer risk, deaths in different sites of bowel cancer.

Public Health Impact: By evaluating O3FA intake (diet and supplement use) and bowel cancer risk, this study has the potential to influence dietary recommendations and O3FA supplement use preventing bowel cancer and improving outcomes following bowel cancer diagnosis. If the project is able to demonstrate a reduced risk of bowel cancer in specific parts of the bowel, it will contribute knowledge enabling a personalised approach to bowel cancer risk reduction and treatment in the future. The findings could also help inform the dose of O3FA interventions in future clinical trials of O3FA treatment of multiple conditions cancer, heart disease and dementia.

To date, no observational study has examined omega-3 polyunsaturated fatty acid (O3FA) intake (both dietary and fish oil supplement [FOS] use), validated and correlated with circulating O3FA values in a significant proportion of the study population, in relation to colorectal cancer (CRC) risk and mortality, taking into account location of the CRC within the colorectum. 

The two main O3FAs, EPA and DHA are found in highest quantities in oily fish, as well as being the main bioactive components of commonly used fish oil supplements (FOS). O3FA have anti-CRC and anti-inflammatory properties in experimental studies and randomised trials of EPA treatment. However, existing epidemiological data of dietary O3FA intake and CRC risk is inconclusive, perhaps due to a lack of recording of FOS use and/or incomplete validation of O3FA intake (select case-control studies have measured O3FA levels in small sub-populations only).

This study aims to evaluate O3FA intake (dietary fish intake and FOS use), validated and correlated with nuclear magnetic resonance (NMR) metabolomic biomarker (O3FA and DHA variables) data (total n=120,000) in relation to CRC risk and mortality, taking into account CRC location within the colorectum.

Scope extension:

It has recently been reported that a genetic polymorphism in a gene that is important for O3FA metabolism (rs66698963) predicts the colorectal polyp prevention efficacy of the O3FA eicosapentaenoic acid (EPA). Therefore, the additional scope of the project will be to investigate a gene (FADS2 indel rs66698963) x diet (oily fish and FOS interaction) for CRC risk using UK Biobank whole genome sequencing data.