Lung cancer is one of the largest health burdens worldwide: in Canada alone, lung cancer causes more cancer-related deaths than breast, colon, and prostate cancers combined. Smoking cessation programs have been highly successful, and the population of former smokers in Canada is well over seven million. Unfortunately, while quitting smoking is a proactive step, former smokers are still at risk for developing lung cancer. This cancer risk in former smokers will remain one of Canada's most significant health concerns for the next 50 years. The molecular mechanisms responsible for the development of lung cancer in former smokers are not known. Recent studies have shown that although the majority of smoking-induced genetic damage returns to normal after smoking cessation, some genes are permanently damaged and never return to the pre-smoking state. Some of these irreversible genes are likely those that act as the gatekeepers for cancer development. Dr. Ewan Gibb's research project will identify the genes in former smokers which do not return to normal after smoking cessation. He will be using integrative genomics to compare samples from former smokers with cancer and those without. This information will help Dr. Gibb understand why some former smokers go on to develop lung cancer while others remain cancer-free despite similar changes in lifestyle. This set of irreversibly damaged genes can serve as novel targets for anticancer therapies or may be developed as diagnostic markers for early detection of lung cancer while therapies are still effective.