CHRNA4 and cancer: This mechanism could provide direct carcinogenesis of nicotine and nicotine-metabolites to all cells that express the nAChR, particularly in carriers of the variants that are associated with tobacco smoking and cancer.145–148 Following the idea that inhaled nicotine could produce carcinogenic molecules in human users, an untargeted metabolomics analysis of urine demonstrated a trend of increased carcinogen biomarkers in the samples of a relatively small cohort of vapers (n = 34 vs. n = 45 non-users).149