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Haplotypes with frequencies less than 5% were combined into a single group. We also tested for interactions among significant SNPs in different genes with a cross product term. We tested whether cotinine could be a confounder of the SNP-NNAL association, (since some of the same enzymes (CYP2A6, UGT2B10 and CYP2A13) also metabolize nicotine to cotinine). We tested the associations of cotinine http://www.selleckchem.com/products/z-vad-fmk.html with each of the SNPs controlling for nicotine and packyears, and tested the association of cotinine with NNAL, using all subjects and in controls alone. Biomarkers were log-transformed to meet the normality assumption with cotinine as the outcome in this analysis alone. For the SNPs significantly associated with cotinine, we included sqrt-cotinine in the model (with sqrt-nicotine and other variables previously mentioned) as a confounder of total NNAL outcome. Ninety-two Caucasian samples were analyzed for total NNAL, total nicotine, total cotinine and for creatinine. Creatinine was determined for all samples. For total NNAL, four samples (all cases) were not determined due to co-eluting peaks and 14 samples (12 cases) were at the LOD and so were replaced with 0.7 pmol/ml. For total nicotine only one sample, a control, was not determined due to co-eluting peaks. The same sample was not determined for cotinine, in addition to another case. Since the undetermined samples for nicotine and cotinine did not overlap for NNAL, our effective sample size controlling for nicotine was 87 (35 lung cancer cases and 52 controls) and for our cotinine analysis was 86. Sqrt-total NNAL was correlated with sqrt-cotinine http://www.selleck.cn/products/XL184.html (Spearman �� = 0.82 in controls, 0.37 in cases) and sqrt-nicotine (spearman �� = 0.74 in controls, 0.14 in cases). For the 87 samples analyzed with complete total NNAL and nicotine (Table 2), there were 48 females and 39 males with ages ranging from 33 to 77 with a median of 62 years. Participants smoked 4 to 60 cigarettes per day (CPD) with a median of 20. There were no missing values for age, sex or CPD. Age, gender and sqrt-packyears http://www.selleckchem.com/products/ly2157299.html were not significant variables predicting urinary sqrt-total NNAL when sqrt-nicotine was included. Sqrt-nicotine was highly significant predicting a 0.018 (0.014�C0.023) pmol/mg creatinine unit increase in sqrt total NNAL for every ng/mg creatinine increase in sqrt-nicotine at p