Lung cancer is the leading cause of cancer death in the United States. Cigarette smoking causes 85% of lung cancer deaths, however only about 15% of smokers will develop lung cancer in their lifetime. Genetic variations can modify the effect of the exposure to cigarette smoke. Our lab studies genetic variations in enzymes that detoxify potent carcinogens from cigarette smoke (including nitrosamines such as NNK and NNAL). We have identified a whole gene deletion polymorphism in a carcinogen metabolizing gene (UGT2B17) that is associated with decreased carcinogen metabolism, and increased risk for lung cancer, and have identified a gender specific disease risk. Many studies suggest that women have greater susceptibility than men for lung cancer per amount of smoking exposure. UGT2B17 metabolizes both carcinogens and sex-hormones, so this gene deletion may play a role in the gender-differences in lung cancer risk. This seminar will discuss correlations of DNA genotype, with RNA expression and enzyme activity, resulting in increased risk for lung cancer in individuals with particular genotypes.