World Cancer Research Fund International is a leading supporter of systematic research on cancer prevention related to diet, weight and physical activity.
The link between cancer and diet-induced zoonotic infections with agents of so far unknown pathogenic potential is of utmost importance to expand our limited options for preventive and therapeutic cancer intervention.
We are delighted to test exposure of mice towards bovine meat and milk factors (BMMF) – which were hypothesised as drivers of indirect carcinogenesis for a set of human cancers including colon and breast cancer – based on BMMF mouse models to understand the effect of BMMF on chronic inflammation and cancer induction as a basis to test systematic intervention. – Dr Timo Bund
Grant title
Understanding the role of bovine meat and milk factors (BMMF) in chronic inflammation and colorectal cancer
Background
Cow milk (bovine milk) is an important part of human diet and broadly associated with increased health. Negative effects are known including lactose intolerance and dairy allergy, and some specific milk components (microRNAs) are suspected to indirectly cause cancer. 100 different types of viruses or infectious molecules in bovine meat and milk samples have been identified, called bovine meat and milk factors (BMMF). BMMF are active in human cells, and replicate and produce proteins.
Current data supports that BMMF enter and infect humans in the very early age and further accumulate in immune cells of the colon, which orchestrate the defence against infections. Long-term consumption may result in chronic inflammation in the colon, damaging the cells that may develop into tumour precursors. This causes an elevated risk for the development of colon cancer commonly 40–70 years after first infection with BMMF.
Aims and objectives
Although we know that BMMF intake can cause chronic inflammation, and thus cancer, we do not know how BMMF enter and persist in cells, which changes are induced and how we could prevent it. These questions need to be addressed in a model system that resembles the human host. As human models are largely unavailable at this stage, a BMMF mouse model represents the optimal test system.
How it will be done
We will compare BMMF presence in mice fed with different diets: standard, bovine milk and BMMF-enriched diets. We will analyse the reaction of the immune system to evaluate the inflammation state, monitor BMMF load and conduct experiments to understand which mechanisms they induce.
In addition, we will test whether interventions for reduction of BMMF and chronic inflammation work.
Potential impact
This project is essential to understand how BMMF induce chronic inflammation, and if preventive and therapeutic approaches can decrease the level of BMMF and chronic inflammation. This knowledge would allow us to later use BMMF-based therapies to prevent or cure cancer.
The model would not only apply to treatment and prevention of colon cancer but also breast, lung, prostate, oesophagus, stomach and ovarian cancer, where anti-inflammatory drugs are used for reduction of cancer risk, pointing towards an association with chronic inflammation.