Grant: Doctoral: Vanier Canada Graduate Scholarships

Lung cancer is the number one cancer killer in the world and up to 25% of cases occur in never smokers (NS). Soon, due to the continued promotion of smoking cessation as a prevention strategy, most lung cancers will be found in NS. A multitude of genetic alterations contribute to lung cancer development and some occur differentially in smokers and NS. This suggests lung cancers in these cohorts are genetically distinct. As the proportion of lung cancer in NS is expected to rise, research to identify distinct genetic events driving lung cancer development in this group is required to improve the poor prognosis for these patients. The goal of my research is to address the hypothesis that lung cancer in NS develops due to genetic alterations distinct from those in smokers. I aim to identify DNA alterations casual to lung cancer development specifically in NS. I will use a genomics approach to screen NS lung tumours. Using tumour DNA I will identify alterations in three dimensions: gene dosage, DNA methylation, and allelic makeup. Integration of my findings with expression profiles generated from tumour mRNA will reveal alterations affecting gene expression. Alterations eliciting such biological effects likely contribute to lung cancer development because they disrupt tightly regulated expression levels and cell signalling networks, leading to cancer initiation. Comparison of my findings in NS and smoking-induced lung cancers will reveal casual DNA alterations specific to NS. If my hypothesis is correct, the genetic alterations I find in NS lung cancers may represent novel diagnostic markers or therapeutic targets. My findings will directly improve the health of Canadians by providing evidence that suggests NS and smokers with lung cancer should be managed differently, and by revealing genetic targets for the development of novel diagnostic and therapeutic strategies. These discoveries will lead to a better prognosis and standard of care for NS lung cancer patients.