Risk and progression of colorectal cancer in people with type 2 diabetes
Lead Research Organisation:
University of Bristol
Department Name: Bristol Medical School
Abstract
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:
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.
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:
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.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013794/1 | 01/10/2016 | 30/09/2025 | |||
| 2283235 | Studentship | MR/N013794/1 | 01/10/2019 | 31/03/2023 | Andrei-Emil Constantinescu |