This project aims to determine the clinical, pathological, molecular and lifestyle characteristics of colorectal cancers to enable future strategies for the prevention and early detection.
Changes in the gut microbiome composition are known to be a significant risk factor for developing colorectal cancer (CRC).
In recent years, several genotoxin-producing gut bacterial species including Escherichia coli (pks+E.coli), Fusobacterium nucleatum (F.nucleatum), and Enterotoxigenic Bacteroides fragilis (ETBF) have been directly linked to CRC development through initiation of DNA damage to host genome and epigenome.
Determining which CRCs are caused by these genotoxic bacteria and how their presence can be modulated by environmental and lifestyle exposures (e.g. smoking, obesity, dietary behaviours, alcohol consumption) will enable future strategies for the prevention and early detection of bacteria-related CRC.
This project aims to determine the clinical, pathological, molecular and lifestyle characteristics of CRCs that have tumour infiltrating carcinogenic gut bacterial species (pks+E.coli, F.nucleatum and ETBF), in a large population-based cohort of CRC-affected people.
- Aim 1: Determine, for the first time, the prevalence of pks+E.coli, F.nucleatum and ETBF in unselected CRCs using a novel, high-throughput screening assay.
- Aim 2: investigate the clinical, pathological, molecular and lifestyle characteristics of these bacteria-related CRCs compared with CRCs absent of these bacteria.
- Aim 3: Investigate the unique and specific patterns of DNA damage caused by pks+E.coli, F.nucleatum and ETBF in CRC tumour DNA through assessment of genome-wide DNA methylation and somatic mutation data.
The outcomes from this project will determine the prevalence of key carcinogenic gut bacteria in CRC. This project will develop expertise in molecular genetics/biology, histology, bioinformatics and statistical analysis. A stipend for this project is available to the selected student.
Contact and more information
Associate Professor Daniel Buchanan
Dr Eric Joo
Dr Mark Clendenning
Colorectal Oncogenomics Group
University of Melbourne Centre for Cancer Research and Department of Clinical Pathology
Level 10, Victorian Comprehensive Cancer Centre