Molecular basis underlying cigarette smoking-induced lung cancer

Lung cancer is the leading cause of cancer deaths in the United States. It is well established that cigarette smoking can cause lung cancer, which is well exemplified in Kentucky, as Kentucky leads the nation not only in tobacco use and production, but also in lung cancer incidence and mortality rates. However, the molecular basis for cigarette smoke-induced lung cancer is not fully understood. Like all other cancers, lung cancer is characterized by instability of the genetic materials, i.e., DNA. Because DNA repair mechanisms are essential for maintaining the stability of the genetic materials, we therefore hypothesize that cigarette smoking inactivates DNA repair, which leads to DNA instability and lung cancer. In this application, we propose experiments to understand how cigarette smoking inhibits DNA repair and whether or not a defective DNA repair system is associated with cigarette smokers. A successful completion of the proposed study will not only reveal the molecular basis underlying cigarette smoke-caused lung cancer, but also provide novel biomarkers for lung cancer screening and/or risk assessments.