MR is a statistical method, a way to analyse data, that uses people’s genetic variation – in other words the different genes that we carry and which form our unique footprint.

This variation helps to approximate a dietary exposure independently of other dietary exposures and – ultimately – pinpoint a causal effect to a specific nutrient. This effect will be distinct from other factors that might be correlated with that nutrient, as part of people’s diet or lifestyle.

This is possible because, if there is a lot of data available, at a population level that unique footprint is less likely to be associated with environmental factors, which are precarious and may confound the associations found from observational studies.

World Cancer Research Fund supports many MR projects and the research community that delves into this field to shed light on the causal relationship between nutrition and multiple cancer sites.

We have already funded 9 projects in the UK, France, Japan, Germany and Sweden. More recently, we have  supported the MR in Nutrition and Cancer workshop, a working group from experts in the field.

A position paper from that workshop provides two key outputs:

• an overview of MR, discussing applications and providing examples of MR studies in nutrition and cancer.
• the limitations of the tool, and how to overcome those to translate findings from MR studies into nutritional recommendations and policies for cancer prevention, that will be used from the scientific community around the world.

Challenges of Mendelian randomisation

Of course, as with every statistical method, MR comes with its own challenges. You need studies with large sample sizes to avoid biases, which is often difficult to achieve unless different teams work together and pool data from smaller studies.

It’s crucial to have enough data to showcase a robust association between nutritional traits and genetic variation in the population.

This association, in turn, increases our level of certainty in the findings and their interpretation – which is called statistical power – and the chances of detecting relationships of modest strength that are not obvious.

Another challenge originates from the limited understanding of the biological mechanisms that underpin the detected associations and this requires caution when interpreting the findings.

Scientists have achieved great progress in developing methods to mitigate those challenges, such as performing more sensitive analyses, and forming large consortia and international collaborations. In an attempt to expand the focus of MR studies beyond populations of European ancestry to tailor findings to other populations as well, they have also increased the number of trans-ethnic databases.

Nutrition is a puzzle of complex and interconnected relationships, but the scientific community is devoted to unravelling the mystery. The aim is to give us clear explanations and modifiable nutritional risk factors for cancer development and progression, and the belief is that MR has the potential to contribute significantly to those efforts.

This is of particular importance to us as we embark on the next phase of the Global Cancer Update Programme. MR will complement existing methodologies for evidence synthesis and interpretation, and will equip us with robust evidence and up-to-date recommendations for specific cancer sites.

Our MR grants

Bethany van Guelpen
> The role of inflammation in the link between obesity and colorectal cancer

Michael Leitzmann
> Physical activity, sedentary behaviour and cancer risk in people with comorbidities

Laure Dossus
> Exploring the link between obesity and endometrial cancer

Konstantinos Tsilidis
> Why does food increase or decrease the risk of colorectal cancer?
> Comprehensive assessment, validation and causal identification of dietary exposures and cancer risk

Sarah Lewis
> How does physical activity lower the risk of cancer?
> Identifying which nutrients may cause or protect against prostate cancer

Shoichiro Tsugane
> The protective effect of consuming polyphenols on colorectal cancer risk in Japan

Emma Vincent
> Are metabolites associated with obesity causing colorectal cancer?

Paul Brennan
> The impact of obesity and insulin on cancer risk