Project 466745

With rapid legalization and decriminalization of cannabis, there is a growing need to understand its specific effects, particularly through smoking, the main method of consumption. Current literature on cannabis smoke primarily consists of clinical studies with conflicting results. Thus, there is a lack of controlled experimental studies investigating the effects of cannabis smoking on adverse lung health outcomes, specifically lung cancer development. This is an important consideration as the chemical composition of cannabis smoke is qualitatively similar to that of tobacco, and it has been demonstrated that routine screening of individuals who heavily smoke tobacco improves survival outcomes through early detection.This study aims to explore how cannabis smoke exposure mediates hallmark processes involved in lung cancer initiation and development. I hypothesize that cannabis smoke induces mutations and shifts gene expression to promote tumorigenesis. To test this, I will expose both human lung epithelial cells and mice to cannabis smoke at levels comparable to regular human consumption. Mutational patterns and gene expression changes induced in the cannabis smoke exposed cells and mice will be assessed through DNA and RNA sequencing, respectively, and compared to those of tobacco smoke and room air as a control. The mutational signatures and gene expression profiles resulting from cannabis smoke exposure will then be cross-referenced with the analysis of human tumours collected from patients with known cannabis exposure.Overall, this study will rigorously determine the effects of cannabis smoking on lung cancer development. This knowledge can be applied to assess the risk of cannabis smoking as well as to improve screening protocols aimed at the early detection.