Lung cancer is a disease characterized by the uncontrolled growth of cells in the lung tissues. This growth can lead to metastasis into adjacent tissues and infiltration beyond the lungs. Most primary lung tumors arise from epithelial cells. Lung cancer is the most common cause of cancer-related death in men and women and is responsible for 1.3 million deaths annually worldwide, as of 2004 (37). The main types of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Depending on the type of lung cancer, treatment varies: NSCLC is sometimes treated with surgery, while SCLC often responds better to chemotherapy and radiation (38). The most common cause of lung cancer is long-term exposure to tobacco smoke (39). The onset of lung cancer in nonsmokers, which accounts for approximately 15% of cases (40), is often attributed to a combination of genetic factors (41, 42), radon gas (43), asbestos (44), and pollution atmospheric (45-47) including passive smoking (48, 49). Undoubtedly, lung cancer caused by tobacco smoke is influenced by interindividual genetic variability which in turn influences the metabolism of tobacco smoke carcinogens, similar to the genetic impact on the metabolism of therapeutic agents. In this case, however, variable metabolism results in variable levels of harmful DNA adducts and, ultimately, cancer-causing mutations, rather than adverse effects, as is the case with chemotherapy treatments. The use of tobacco products continues to be an immense public health problem. problem, and it could be argued that it is the largest voluntary source of human exposure to carcinogens in the world. However, over the last 20 years much progress has been made, not only in understanding the mechanisms of tobacco carcinogenesis, but genetic variations within this gene are beginning to emerge, further underscoring its importance (64-67). Both environmental and genetic factors play a role in the development of most diseases, and therefore it is important to understand the interactions between these factors. In all discussions of environmental exposure (environment refers to any external agent, including drugs), the dose to which an individual is exposed is critical. Therefore, it is crucial to understand gene-environment interaction. The idea that genetic variants modify cancer risk following exposure to various levels of external agents first came from studies of metabolic genes in environmental carcinogenesis ( 68 , 69 ). A part of this thesis investigates the gene-environment relationship in lung cancer by studying variations in known environmental exposure pathways..