Understanding the link between colorectal cancer and obesity through metabolic profiling
This project aims to determine ‘metabolic signatures’ associated with obesity and assess their link with colorectal cancer, using untargeted metabolomics – a technique that allows simultaneous assessment of thousands of metabolites in blood.
Institution:International Agency for Research on Cancer (IARC)
Grant title: Understanding the mechanisms linking obesity with colorectal cancer risk using metabolomic profiling
In this project, we will use untargeted mass spectrometry-based metabolomics to identify circulating metabolites associated with obesity, weight loss and risk of colorectal cancer. We expect the results to greatly improve our understanding of the molecular mechanisms underlying the obesity-cancer relationship, and of the metabolic effects of risk reduction measures achieved through different weight loss interventions. – Dr Pekka Keski-Rahkonen
Obesity is known to be an important risk factor for colorectal cancer. However, the mechanisms connecting obesity with colorectal cancer are not well understood.
Intentional weight loss reduces the risk for some cancers, and studying how weight loss can impact the metabolites known to be involved in colorectal cancer development can help us to find key metabolic pathways involved in obesity and cancer, and may elucidate novel strategies for cancer prevention.
Aims and objectives
The suggested project aims to determine “metabolic signatures” associated with obesity and to assess their link with colorectal cancer, using untargeted metabolomics. Untargeted metabolomics is a technique that allows simultaneous assessment of thousands of metabolites in blood. The project will also explore how the obesity-associated metabiltes respond to weight reduction.
How it will be done
By using data on thousands of blood metabolites from 1,575 cancer-free participants from a study called EPIC, we will search for association of metabolite concentrations with the participants’ body mass index (BMI) and other measurements of obesity.
The obesity-associated metabolites will then be tested in a separate series of 280 samples from EPIC, and finally assessed for their association with a risk of getting colorectal cancer using a case-control study within EPIC.
For the case-control study, blood samples were collected prior to cancer diagnosis, with 1,121 participants diagnosed with colorectal cancer several years after blood collection. By comparing the levels of obesity-associated metabolites between cases and controls, we will assess the colorectal cancer risk linked to them. This allows us to better understand which obesity-related mechanisms may be involved in colorectal cancer development.
We will then more deeply study how the observed colorectal cancer-associated metabolites are involved in obesity by using data from 4 studies on weight loss where samples were collected pre- and post-intervention. We purposely chose studies with different interventions including surgical, pharmaceutical and lifestyle alteration, to assess how the observed colorectal cancer risk-associated metabolites behave with weight loss to study the potential metabolic pathways linking obesity with cancer risk, and if these can be modified through weight reduction.
The proposed study will identify blood metabolites associated with obesity and different weight loss strategies, and how these metabolites are linked with colorectal cancer risk. This new scientific knowledge will enhance our understanding of the potential underlying mechanisms and metabolic pathways at the intersection of obesity and colorectal cancer development. Our results can potentially provide guidance for policies targeted towards colorectal cancer prevention.