Grant: Project Grant

Lung cancer is the highest lethality Canadian cancer. It is overwhelmingly caused by tobacco smoke and/or inhalation of radioactive radon gas. Radon emits ionizing radiation that can cause serious health effects depending on dose and type. Relative to photon radiation (such as x-rays), the alpha particles emitted by radon produces much more disease-causing, complex DNA damage. Radon is very prevalent in our environment and is the main cause of lung cancer in the ~20% of patients who are never-smokers, encompassing >25,000 North Americans per year. Despite this, technological limitations to conveniently deliver alpha particles repetitively, in low doses and in an affordable, high throughput manner have constrained research on this topic. Consequently, our knowledge of why some people, tissues and cell types are susceptible to radiation is mainly derived from high dose, acute exposure photon research. This is problematic, as health protection risk models are being built on data derived from photon studies that have an ambiguous relevance to what we are most exposed to in life, which are alpha particles via radon inhalation. To resolve this, our lab has developed a next-generation, high throughput alpha particle irradiator able to deliver adjustable, low doses that reflects what is happening to Canadians in our environment. We will use this to define - in exquisite molecular detail - alpha particle effects on the stability of our DNA and changes that can lead to cancer. This project will be the first to employ a high-throughput approach to systematically solve key alpha particle biology questions. This is important as, while radon causes thousands of lung cancer diagnoses annually, knowledge to meaningfully intervene before clinical manifestation is unacceptably low. We will be impactful by building the essential knowledge to identify those at risk of radon-induced cancer based on novel, next-generation methods fuelled by expert knowledge of DNA damage repair biology.