B4361 - Young onset colorectal cancer and childhood exposures to the microbiome YOUTHCLUB - 18/08/2023

B number: 
B4361
Principal applicant name: 
Kaitlin Wade | Bristol Medical School, University of Bristol (United Kingdom)
Co-applicants: 
Title of project: 
Young onset colorectal cancer and childhood exposures to the microbiome (YOUTHCLUB)
Proposal summary: 

Colorectal cancer incidence in individuals younger than 50, referred to as early-onset colorectal cancer (eoCRC), has doubled in many countries. Over the next decade, deaths due to eoCRC are expected to rise globally, with eoCRC accounting for over 20% of all colorectal cancers and becoming the leading cause of cancer-related deaths in 20-49 year olds. However, the factors leading to this increase are uncertain. The gut microbiome, which comprises millions of bacteria, fungi and viruses that are housed naturally within our digestive system, may influence the development of colorectal cancer, whereby some microbiota play a role in inflammation, DNA damage and production of cancer-promoting molecules. Recent studies have shown that there are specific genetic mutations associated with colorectal cancer risk, which occur more often in people of younger ages than in older ages. These mutations are also caused by the toxin called colibactin, which is produced by certain gut microbial bacteria. Our study aims to understand whether these bacteria, if present in early life, cause these mutations within our DNA (via colibactin production) and therefore increase the risk of eoCRC.

Impact of research: 
The project is focused on unravelling the role of the childhood microbiome in the development of early-onset colorectal cancer (eoCRC). The proposal focuses on eoCRC because (i) the incidence and mortality due to eoCRC are rapidly raising, making this cancer type a leading cause of cancer-related deaths worldwide; (ii) the rise in eoCRC cases is not limited to any specific region or population, thus, making it a global health issue; (iii) there are no accurate diagnostic methods for detecting eoCRC and there are no effective intervention approaches for preventing eoCRC; (iv) prior work provides strong evidence supporting the role of the paediatric microbiome in eoCRC, which warrants multiple avenues of investigation; and (v) there is no similar evidence of the neonate microbiome being involved in any other type of human cancer. This project will therefore provide a novel global multi-omic resource for studying normal colorectal epithelium and eoCRC, comprehensive understanding of the role of early life microbiome-driven mutagenic and carcinogenic exposures in the development of eoCRC, an experimental map of the mutagenic and carcinogenic roles of the microbiome and an evaluation of the potential opportunities for intervention.
Date proposal received: 
Wednesday, 9 August, 2023
Date proposal approved: 
Thursday, 10 August, 2023
Keywords: 
Multi-disciplinary - bioinformatics, epidemiology (most relevant for the work being conducted with ALSPAC), mouse and organoid models, mathematical modelling and artificial intelligence., Cancer, Gastrointestinal, Cell culture, Computer simulations/modelling/algorithms, DNA sequencing, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Childhood - childcare, childhood adversity, Genomics, Microbiome, Cancer