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The role of diet, nutrition, and adiposity in colorectal cancer development


   Bristol Medical School

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  Dr E Vincent, Dr James Yarmolinsky  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Colorectal cancer (CRC) is the third most common cancer worldwide and constitutes around 10% of all cancer deaths, making it the second commonest cause of cancer mortality. Over the last 25 years, the overall incidence of CRC has gradually declined, partially attributable to societal changes towards healthier lifestyle choices. Despite this overall decline, alarmingly, CRC cases have increased in individuals aged between 20-39 years old. These patients have poor 5-year survival rate (<60%) emphasising the urgency for a greater understanding of what causes CRC so that we might prevent it arising in the first place.

4 in 10 UK cancer cases are thought to be preventable through lifestyle changes and obesity is now an established risk factor for CRC development. Weight-loss by dietary intervention as a strategy to reduce CRC risk of is an active area of research. For example, it has been found that individuals who consume high amounts of simple sugars may have a greater risk of developing CRC, conversely, those consuming a ketogenic diet, with low carbohydrate intake, may have a reduced risk of developing this disease. Adipose tissue likely plays a role in promoting tumourigenesis but the exact mechanisms underlying this relationship are incompletely understood.

Aims and objectives

Research question: Can manipulating dietary sugar and carbohydrate intake reduce CRC risk by altering adipose tissue biology?

Hypothesis: We hypothesise that manipulating dietary sugar and carbohydrate intake will influence CRC risk by altering adipose gene expression.

Aims:

  1. To determine gene expression changes in adipose tissue in response to the dietary interventions. By analysing samples and data collected as part of a randomized control trial (RCT).
  2. To determine whether these gene expression changes influence colorectal cancer risk. Using techniques in genetic epidemiology.
  3. To explore how these gene expression changes impact CRC development. Using cellular models of CRC.

Methodology

Conducting randomized control trials (RCTs) of dietary interventions to determine the impact on cancer risk is challenging, the long-time frame and large number of participants needed makes these studies prohibitive. To combat this, we propose to use data and samples collected as part of a 12-week dietary intervention trial (manipulating sugar and carbohydrate intake) on healthy, cancer-free individuals. We will measure biological changes in the participants adipose tissue samples and then investigate whether these changes impact CRC risk using a genetic epidemiological method called Mendelian randomization (MR). MR will allow us to use the biological changes we observe in the 12-week RCT as proxies to investigate whether the dietary intervention could impact CRC risk.

For dietary changes to impact cancer risk, we would expect to observe changes in gene expression in the body’s cells and tissues, indicating that the dietary change impacts cell biology. We will therefore measure gene expression in adipose tissue using RNA-seq and use MR to predict whether changes to gene expression (caused by the dietary intervention) impact risk of CRC. Upon identifying gene expression changes that cause CRC we will investigate how these changes might impact CRC development using laboratory cellular models of CRC.

Apply for this project

This project will be based in Bristol Medical School - Translational Health Sciences.

Please contact for further details on how to apply.

Apply now!


References

Brennan, P., & Davey Smith, G. Identifying Novel Causes of Cancers to Enhance Cancer Prevention: New Strategies are Needed. JNCI. 10.1093/jnci/djab204
Lauby-Secretan, B., et al. Body Fatness and Cancer — Viewpoint of the IARC Working Group. N Engl J Med. 10.1056/NEJMsr1606602
Davey Smith, G., & Shah, E. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? IJE. 10.1093/ije/dyg070
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