Investigating the role of dietary fructose in the development of early-onset colorectal cancer

Project Background

This project will investigate the role of fructose in the development of early-onset colorectal cancer (EOCRC) in adults <50 years. Alarmingly, the incidence of EOCRC in the UK is increasing rapidly. Because of this, defining and understanding the differences in EOCRC compared to late-onset CRC is a question of critical importance. We are currently unable to prevent, predict or optimise treatment for people with EOCRC for the simple reason that we do not understand the biology of this disease completely.

Drinking sugar sweetened beverages (SSBs) has been implicated in risk of developing EOCRC. Consistent with this, fructose, a major constituent of SSBs, has itself been implicated in CRC development and metastasis. The mechanisms remain poorly understood, however, there is evidence that they may be mediated by altering chromatin accessibility and epigenetic modifications in colon tissue. This could result in changes in gene expression driving the biology of a developing tumour. 

Project Aims

The overarching aim of this project is to understand how exposure to dietary fructose might influence EOCRC development through impacting chromatin accessibility and downstream gene expression. 

Aim 1. Determine whether genes involved in fructose metabolism play a causal role in the development of EOCRC.

Aim 2. Determine whether fructose alters tumour cell phenotype and chromatin accessibility.

Aim 3. Investigate whether changes downstream of fructose exposure are causal for EOCRC development. 

Project Methods

This is an interdisciplinary project using techniques in both genetic epidemiology and laboratory-based cell biology. As such, upon completion of this PhD, the student will possess a highly desirable and versatile interdisciplinary skill set.

Genetic epidemiological techniques, such as Mendelian randomization, will be used to determine whether expression of fructose metabolism genes can influence EOCRC development. The student will use the largest genetic dataset of human EOCRC available and receive training at the MRC Integrative Epidemiology Unit and the International Agency for Research on Cancer in Lyon, France.

Training in techniques in cancer cell biology will allow the student to determine how exposure to fructose alters tumour cell phenotype using both cell lines and state-of-the-art patient derived organoids models. Data collected will guide and inform further studies using genetic epidemiological techniques. 

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Population Health Science and how to apply.