Risk and progression of colorectal cancer in people with type 2 diabetes.

The University of Bristol is offering a 3.5 year full time PhD in research around Population Health to start in 2019. This studentship is funded through GW4BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,777 p.a. for 2018/19, updated each year).
Additional research and training funding is available over the course of the programme. This will cover costs such as research consumables, courses, conferences and travel. Additional competitive funds are available for high-cost training/research.
The studentship is based at the Bristol Medical School. For further information please see the website below.
http://www.bristol.ac.uk/medical-school/
Type 2 diabetes is associated with increased cancer risk. The aim of the project is to identify and investigate causal pathways that link type 2 diabetes to colorectal cancer. This interdisciplinary project will involve epidemiological analysis of multi-omics datasets and molecular cancer cell biology techniques.
Rationale: People living with type 2 diabetes have abnormal levels of circulating metabolites in their blood. This results in systemic exposure of cells and tissues to an abnormal and unregulated metabolic environment. Such exposure is likely intrinsically linked to the probability a cancer develops and the cancer cell phenotype. This is because carcinogenesis requires that tumours reprogram their metabolic pathways to adapt to their metabolic environment to satisfy demands of chronic cell proliferation. Given the abnormal serum metabolome in people with type 2 diabetes and the potential impact on tumorigenesis it is unsurprising that type 2 diabetes is associated with an increased risk of developing cancer at several sites. However, the inherent heterogeneity of type 2 diabetes makes it challenging to characterise positive associations as causal. This proposal is intended to investigate the impact of the dysregulated metabolic environment characteristic of people with type 2 diabetes on the incidence and progression of colorectal cancer. It will also investigate whether drugs taken to treat type 2 diabetes can reduce colorectal risk by modulating metabolism. Aims & objectives: We aim to understand why people with type 2 diabetes have an increased risk of colorectal cancer. To investigate this, we will focus on the levels of circulating metabolites that are altered in people with type 2 diabetes. 3 main aims: 1) To identify the circulating metabolites that are altered in people with type 2 diabetes and identify which of these metabolites are causally associated with colorectal cancer risk and progression. 2) To investigate how certain metabolites might increase risk of cancer. 3) To investigate how type 2 diabetes drugs might reduce colorectal cancer risk by modulating cellular metabolism. Methods Here, we will use methods in genetic epidemiology and in particular Mendelian randomization to determine which metabolic traits characteristic of type 2 diabetes are causal for colorectal cancer (Aim 1). Laboratory based methods will be used to investigate the mechanisms underlying the associations between levels of circulating metabolites and cancer risk (Aim 2). To investigate the role of type 2 diabetes drugs in colorectal cancer incidence and progression (Aim 3) we will start by interrogating drug prescribing data to understand how these drugs are prescribed, at what stage of type 2 diabetes people are taking them and the duration of time they are exposed to them. We will then investigate how type 2 diabetes drugs might reduce cancer risk by influencing both whole body metabolism (this will be investigated using clinical trial samples) and colorectal cell metabolism (this will be investigate using laboratory techniques in cancer cell biology)
Candidate requirements: Applications are welcome from high performing individuals across a wide range of disciplines closely related to natural sciences, biostatistics, genetics, bio-chemistry, mathematics and computer science who have, or are expected to obtain, a 2.i or higher degree. Applications are particularly welcome from individuals with a relevant research Masters degree.

How to apply: Please make an online application for this project here: https://www.findaphd.com/search/PhDDetails.aspx?CAID=2940&LID=287

Contact: Emma Vincent [Email Address Removed]