Genetic Variability In Tobacco-Specific Nitrosamine Nnk To Nnal Metabolism

Introduction: Tobacco-specific nitrosamine (TSNA) NNK metabolites NNAL and NNAL-gluc) together, (total NNAL), have recently been shown to be good predictors of lung cancer risk, years prior to diagnosis. However, the inter-individual variability in the metabolism of NNK evaluated by the total NNAL output could be explained in part by genetic variability in the genes of NNK metabolism. We sought to determine the contribution of several genetic polymorphisms to total NNAL output by a regression analysis of NNAL levels on genotyping results, controlling for measures of smoking, age and sex.Methods: The study subjects were derived from the Harvard/ Massachusetts General Hospital Lung cancer case-control study. We selected 92 subjects (39 lung cancer cases and 53 controls) smokers at time of diagnosis and urine collection (1992-1996). We tested 77 tagging SNPs in 16 genes related to NNK to NNAL …