Effect of ethanol on eukaryotic genome stability: identification of molecular mechanisms

A staggering 6% of all cancers worldwide are associated with alcohol consumption. The risk of developing mouth and throat tumors, for example, increases dramatically with increasing alcohol consumption. Despite the clear link between ethanol intake and the incidence of specific tumors, the precise toxic effects of ethanol, as well as the exact molecular mechanisms underlying its carcinogenic effects are still not fully understood. This is mainly because ethanol has many different effects on cells, and it is still unclear which of these effects are relevant for cancer development. In this project, we will use an unbiased, stepwise approach to identify cellular targets and map the different processes affected by ethanol. First, we will use the model eukaryote Saccharomyces cerevisiae for an in-depth study of the effects of ethanol on eukaryotic genome stability and determine the underlying molecular mechanisms. Next, we will characterize the effect of ethanol on genome stability and gene expression in human cell lines. This will allow us to determine which pathways are affected by ethanol. Finally, we will identify the type of mutations present in alcoholrelated tumors and determine to which molecular processes these can be linked. Together, these results will increase our understanding of the cellular effects of ethanol and lead to a better insight in the molecular and mutational processes underlying alcohol-induced tumor development.