+44 (0)131 5651 8694
Cancer Research UK Edinburgh Centre
University of Edinburgh
Western General Hospital
Crewe Road South
Edinburgh EH4 2XR
Intestinal tumour modelling and DNA damage: investigating the role of DNA mismatch repair in ethanol induced colorectal carcinogenesis
Ethanol is a known risk factor for colorectal cancer and is classified (along with its metabolite acetaldehyde) as a group one carcinogen by the International Agency for Research on Cancer. We aim to elucidate the mechanisms of ethanol induced colorectal carcinogenesis, in particular in defective mismatch repair driven tumour formation. Colorectal cancers (CRC) have defective DNA Mismatch Repair (MMR) in ~13% sporadic CRCs mostly due to acquired MLH1 promoter methylation and in ~3% CRCs due to inherited MMR gene mutations in Lynch Syndrome. This project will test the hypothesis that the MMR pathway is involved in repair of some of the ethanol/acetaldehyde-induced DNA base adducts and thus ethanol is likely to accelerate dMMR-driven intestinal tumour formation via unrepaired DNA damage.