Identifying molecular mechanisms underlying the effects of ethanol on eukaryotic genome instability
Around 6% of all cancers worldwide are associated with alcohol consumption. For example, the risk of developing head and neck tumors greatly increases with increasing alcohol consumption. Although alcohol consumption is estimated to be the cause of 800.000 cancer cases worldwide, the exact mechanism by which alcohol affects tumorigenesis is not fully understood yet. This also implies that very little is known about the molecular mechanisms that can be targeted therapeutically to eliminate these ethanol-associated cancers. In fact, a detailed characterization of the effects of ethanol on mammalian cells is lacking.
In this project, an in-depth study of the effects of ethanol on eukaryotic genome stability will be performed. To investigate this, a stepwise approach with different experimental systems will be used to identify the molecular mechanisms involved in the carcinogenic effect of ethanol. First, we will use budding yeast as an eukaryotic model system for an in-depth study of the effects of ethanol. Next, we will study the effect of ethanol on gene expression and genome stability in human cell lines. This will allow us to identify the cellular processes affected by ethanol. Finally, we will determine the type of mutations present in alcohol-related head and neck tumors, and try to link these to specific molecular mechanisms. Together, our results will allow a better understanding of how alcohol-related tumors develop and these insights could result in new therapies for patients.