The impact of type 2 diabetes on cancer incidence and progression

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Prof Nicholas Timpson, Dr Emma Vincent, Prof Ann Williams


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Rationale

People living with type-2-diabetes have abnormal levels of circulating metabolites. 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 address which cancers develop as a result of the metabolic environment characteristic of type-2-diabetes and how they do so.

Aims & objectives

We aim to understand why people with type-2-diabetes have an increased risk of 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.
2) To identify which of these metabolites are causally associated with cancer risk and progression.
3) To investigate how certain metabolites might increase risk of cancer.

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 site-specific cancer. We will also investigate how metabolites might increase cancer risk and progression using tissue metabolite analysis. Laboratory based methods will be used to investigate the mechanisms underlying the associations between levels of circulating metabolites and cancer risk. The project is flexible and there will be opportunity for the applicant to conduct laboratory work if they wish to do so, equally a laboratory component is not compulsory if the applicant does not wish to pursue it.

The work will be carried out at the MRC Integrative Epidemiology Unit and in Cellular and Molecular Medicine.

References

Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care 2010;33(7):1674-85.
DeNicola GM, Cantley LC. Cancer's Fuel Choice: New Flavors for a Picky Eater. Mol Cell 2015;60(4):514-23.


Created on Oct. 19, 2017, 1:47 p.m.

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