Understanding the interactions that link diet to cancer

Colorectal cancer (CRC) leads to ≈600,000 deaths globally each year and is one of the major causes of death in the western world. In the UK it is the fourth most common cancer with ~40,000 new cases diagnosed each year (Cancer Research UK). 

The major CRC risk factors are diet, family history and other medical conditions. For example patients with inflammatory bowel diseases (IBDs), such as colitis or Crohn's disease, have a 3-5 fold greater risk of developing CRC. It is therefore a concern that the ~1 in 200 prevalence rate of IBD in the western world is rising, which is at least in part due to diet.

One of the many factors that contribute to the initiation and progression of CRC is inflammation. Inflammation can support tumour development, both directly and indirectly, and tumours can promote a chronic inflammatory environment that results in immunosuppression, which benefits the tumour.

It is well documented that CRCs evolve through loops of deregulated inflammatory stimuli which are sustained by DNA damage signalling pathways and epigenetic re-modelling (DNA methylation). Intensive work in recent years has led to the identification of genes and mechanisms that link diet to changes in the gut microbiota that alter DNA methylation patterns. These alterations drive inflammatory/immune responses which interact with intestinal stem cell and can prevent or promote intestinal disease and cancer. However, to date no studies address all those elements simultaneously. The synergic analysis of such parameters could provide new biological insights and effective biomarkers that could have applications in prevention, molecular diagnosis, prognosis and treatment of intestinal disease and CRC.

Thus, to complement the current reductionist approaches, which examine each of the interacting factors in isolation, there is a requirement for a more holistic approach to unravel how these factors interact. My research focuses on understanding the common mechanisms which link the environment to intestinal disease.