Metabolic health
How can we use the genetic variants associated with obesity-related metabolic complications to better understand cancer risk and progression? Our Metabolic health theme investigates a wide range of adiposity/body composition phenotypes, metabolic traits, and anti-diabetic and anti-hypertensive drugs, on cancer risk.
Highlights include:
Identifying potential targets for breast cancer prevention
Using Mendelian randomization we have found that impaired glucose-dependent insulinotropic polypeptide receptor signalling (reducing glycaemic control; target of the weight loss drug tirzepatide) increases breast cancer risk, indicating a potential prevention target. More information: doi.org/10.1016/j.isci.2023.106848
Cancer Research UK (CRUK) outreach
The Cancer Endocrinology group, led by Dr Claire Perks, holds bi-yearly lab tours for CRUK supporters in the Learning & Research Building, Southmead Hospital. The varied audience includes those that have been affected by cancer directly or indirectly, and members of CRUK. Dr Perks will present the work of the Cancer Endocrinology Group at the Business Beats Cancer Gala Dinner fundraising event for CRUK, complemented by a bespoke video of the group’s work, prepared by a PhD student, Omar Alkahtani.
A novel biomarker of poor survival in colon cancer
Xiaoyu Su, a PhD student in the Cancer Endocrinology group found that high levels of a member of a growth factor family, insulin-like growth factor binding protein-5 (IGFBP-5), is associated with worse overall survival for those with colon cancer. High levels of IGFBP-5 also correlate with high levels of molecules, such as N-cadherin, that enable cancer cells to move from the colon to other parts of the body. IGFBP-5 as anticipated is reduced by agents that inhibit the growth of colon cancer cells.
The Metabolic health theme explores the effect of obesity-related metabolic complications on cancer. Having characterised reliable associations between body composition and cancer risk – and the footprint this risk factor leaves on metabolic measures and outcomes – a major focus is to use genetic variants associated with these intermediate traits to better understand cancer risk. The intermediate traits include body composition, insulin sensitivity and secretion, circulating metabolites, inflammation, microbiome composition and toxic chemicals.
Two-sample Mendelian randomization investigations are enabling us to estimate the effect of metabolic exposures on common cancers. Where results indicate strong genetic evidence, observational studies and preclinical experiments are being conducted in order to triangulate our findings.
This research theme builds on collaborations between groups at the University of Bristol, International Agency for Research on Cancer and the University of Exeter.
