As a physician scientist practising in clinical oncology, I have a tremendous respect for the saying, ‘An ounce of prevention is worth a pound of cure.’
World Cancer Research Fund’s focus on preventable cancer is hugely important, and we are delighted to receive your support for our research into the role of inflammation and the immune response in the link between excess body fat and colorectal cancer. – Assistant Prof Bethany Van Guelpen
Exploring the role of inflammation in the link between obesity and colorectal cancer
Obesity is a risk factor for cancer of the large bowel. It is also a driver of inflammation, which, in turn, can promote cancer development. There are several mechanisms by which excess body fat may cause bowel cancer, one of which may be chronic low-grade inflammation, but the link is only partly understood. The role of inflammation and the immune response in bowel cancer is also complicated. For example, bowel cancer patients with large amounts of certain white blood cells in their tumours have a better prognosis than patients whose tumours are more sparsely infiltrated.
Aims and objectives
In this research project, we aim to conduct a comprehensive investigation of the role of inflammation in the association between obesity and bowel cancer risk, and to discover pathways that might hold promise for personalised prevention. We hypothesise that blood levels of proteins involved in inflammation and the immune response are part of the causal chain between obesity and bowel cancer development.
This project will identify which blood proteins involved in inflammation and the immune response are related to obesity. It will assess whether these obesity-related inflammatory proteins are associated with future risk of bowel cancer, taking into consideration white blood cell infiltration of the tumour. The study will also use genetic data to explore whether these associations are causal.
How it will be done
The study will use two large research cohorts (one Swedish and one multi-centre European) with more than 20 years of follow-up. 1,000 participants who later developed cancer of the large bowel and 1,000 cancer-free control participants will be selected from each cohort. Blood plasma samples from both cohorts will be analysed for proteins involved in inflammation and the immune response to find links between their presence and the risk of bowel cancer. The samples will also be analysed for tumour data on white blood cell infiltration where available.
Obesity-related inflammatory proteins will be studied in so-called Mendelian randomisation analyses to determine if this link is causal.
In order to reduce the impact of obesity on bowel cancer rates, public health strategies to promote healthy body weight will be central, but targeted interventions are likely to be needed. To target obesity, a deeper understanding of the obesity-cancer link is required. The research proposed here will help fill this important knowledge gap.