Cancers of the breast, colorectum, prostate and endometrium are the 2nd, 3rd, 4th and 14th most common worldwide and make up around a third of all cancers. However, we know that the risk of these cancers could be reduced if people ate healthier, were active and maintained a healthy weight. Evidence from World Cancer Research Fund shows that increased physical activity levels may protect against breast, colorectal, and endometrial cancer. Separately, in our own research, we found evidence that physical activity could reduce the risk of prostate, colorectal and breast cancer. However, despite many studies investigating this, it is not clear exactly how physical activity influences our biological systems to reduce cancer risk.
It is possible that physical activity exerts a protective effect against cancer by reducing body fatness, since excess body weight has been consistently shown to increase the risk of many cancers. However, it is also possible that physical activity has a direct effect on cancer risk. There is evidence that physical activity has an effect on several biological systems including immunity, hormones and metabolism, which may consequently affect the risk of several cancers.
Aims and objectives
Based on our previous work and that of other researchers, we believe that being physically active reduces the risk or progression of prostate, breast, endometrium and colorectal cancers. Our aim is to determine the underlying biological reason why physical activity reduces risk. To do so, we will use data from previous studies that evaluated the effect of genetics on hormone levels, proteins, metabolites (small molecules involved in metabolism) and DNA methylation (changes to DNA that turn genes on or off).
How it will be done
The study will be conducted in the Bristol Medical School, University of Bristol and at the International Agency for Research on Cancer both of which have strong track records of research in this area. We will make use very large studies into which people have already been recruited, provided information about their physical activity levels and been grouped based on their genes. Many of these studies have tracked the participants for many years to determine whether they develop cancer and other illnesses.
Firstly, we will look at the distribution of hormones, proteins, metabolites and DNA methylation in relation to physical activity to identify which of these are affected by activity levels. Next, we will look at the distribution of the molecules identified among cancer patients and healthy individuals to determine which molecules could cause or reduce cancer. From this information we can go backwards to determine which biological processes are involved.
Once we have identified molecules and processes which may be important we will use a statistical test called two step Mendelian randomisation, which looks at genetics, to assess whether physical activity alters these molecules and then whether these molecules cause cancer.
This will be a very detailed study, and we will be able to investigate many different biological processes at the same time. In doing this we will advance our understanding of the biological mechanisms influenced by physical activity which can also affect cancer development or progression. The work will help inform public health policies and encourage physical activity promotion to reduce cancer risk. It may also allow people to monitor their cancer risk based on their personal molecular traits, and in doing so may motivate them to do more physical activity.
> Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls (International Journal of Epidemiology, April 2020)