B4045 - Association between adiposity and diabetes with inflammation - 20/04/2022

B number: 
Principal applicant name: 
Vanessa Tan | Integrative Epidemiology Unit, University of Bristol
Lucy Goudswaard, Professor Nicholas Timpson
Title of project: 
Association between adiposity and diabetes with inflammation
Proposal summary: 

Increased adiposity and Type 2 diabetes (T2D) have both been associated with increased risk of developing certain cancers and are both becoming increasingly prevalent globally. Although adiposity, T2D and cancer share many risk factors, the biological pathways linking adiposity and T2D to cancer remain poorly understood.

Chronic low-grade inflammation, characterised by abnormal cytokine production, is associated with both adiposity and T2D. Observational studies have suggested that increased adiposity and hyperglycaemia associated with diabetes induce the production of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6 which have key roles in cancer. This observation has led to the hypothesis that chronic inflammation might be a potential mechanism linking adiposity and T2D to cancer. However, due to the inherent limitations of observational research such as reverse causation and confounding, findings from observational studies need to be interpreted with caution. Furthermore, previous studies have used a single ‘baseline’ measurement of adiposity, T2D and inflammation and cannot fully account for the time-dependent variability in these measurements which may lead to a biased estimation.

Mendelian randomization is an analytical approach where genetic variants reliably associated with risk factors of interest are used as proxy measures to re-estimate the associations between an exposure and an outcome where some of the limitations of observational epidemiology are reduced. In this investigation, we would like to use genetic variants associated with adiposity, T2D and related glycaemic traits to investigate the estimated causal association between adiposity and T2D with inflammatory proteins (measured using the Olink inflammatory panel). We will also use longitudinal measures of inflammatory proteins to investigate whether the relationship between BMI/T2D with inflammation changes over time (across childhood and young adulthood) and potentially identify patterns in the relationship between BMI/T2D and inflammation which may be relevant to cancer development.

Impact of research: 
This project will contribute to the identification of inflammatory proteins associated with adiposity and T2D, and therefore, to our understanding of mechanisms underlying the observed associations between adiposity and T2D with health outcomes such as cancer.
Date proposal received: 
Tuesday, 5 April, 2022
Date proposal approved: 
Wednesday, 20 April, 2022
Epidemiology, Cancer, Proteomics, BMI, Genetic epidemiology, Mendelian randomisation