Are metabolites associated with obesity causing colorectal cancer?

The aim of this research project is to address whether the impact of obesity on colorectal cancer is mediated through changes to the circulating metabolome

  • Topic: Colorectal cancer
  • Institution: University of Bristol
  • Country: United Kingdom
  • Status: Ongoing

“We are very excited to have been awarded this grant from WCRF to investigate the causal link between obesity and colorectal cancer. This grant will enable us to investigate whether changes to the levels of circulating metabolites in people with obesity is responsible for the increased risk of colorectal cancer that is driven by having more body fat”

– Emma Vincent

Background

Obesity is characterised by higher amounts of body fat. There is now strong evidence that having more body fat increases an individual’s risk of developing cancers of the colon and rectum (collectively known as colorectal cancer). Unfortunately, attempts to slow the increase in obesity in the population have so far failed and obesity levels continue to increase. Colorectal cancer is one of the most common cancers in the world and in many countries continues to rise. Because of this, more people will continue to develop colorectal cancer in the coming years. We must therefore find ways of disrupting the underlying link between obesity and colorectal cancer. To do this we must understand the nature of this link – how does obesity cause colorectal cancer? Molecules present at abnormal levels in the blood of people with excess body fat likely form part of this link. These substances, known as metabolites, are sources of fuel and building blocks essential for cells and tissues when present at normal levels. In individuals with obesity the cells of the body are exposed, for perhaps years, to abnormal metabolite levels. This can favour the growth and survival of cancer-initiating cells.

Aims and objectives

We know that having excess body fat increases the risk of developing colorectal cancer. We know that people with obesity have altered levels of metabolites in their blood. What we do not know is whether it is the altered levels of metabolites, and if so which metabolites, that are responsible for the increased risk of colorectal cancer in people with excess body fat. Our proposed research aims to find this out. Our objective is to comprehensively catalogue the metabolites that present during obesity. We will then investigate each of these metabolites to determine whether it contributes to an increased risk of colorectal cancer.

How it will be done

We will carry out our study using a scientific method called genetic epidemiology which uses specific variations in human genes to investigate factors causing disease. We will mainly undertake computer-based analysis of large data sets from existing studies of the general population. Importantly, our approach will enable us to confidently assign cause and effect; in this instance, are the specific metabolite changes characteristic of a person with increased body fat causing colorectal cancer?

Potential impact

This research has the potential to improve the lives of people at risk of obesity-driven colorectal cancer in at least three ways:

  1. Knowing the changes in metabolites in the blood that cause colorectal cancer means that these metabolites could be easily measured and people most at risk could be identified.
  2. Knowing the metabolite changes that are important would allow research to focus on preventing these changes and reduce the risk of colorectal cancer.
  3. Knowing which metabolites cause colorectal cancer will focus treatments onto biological processes that these metabolites are involved in, leading to more people surviving colorectal cancer.

Ultimately, this work will help us better screen for, prevent, and treat cancers triggered by higher body fat.