title: Nicotine metabolite ratio predicts smoking topography and carcinogen biomarker level.
abstract: BACKGROUND
  Variability in smoking behavior is partly attributable to heritable individual differences in nicotine clearance rates. This can be assessed as the ratio of the metabolites cotinine and 3'-hydroxycotinine (referred to as the nicotine metabolism ratio; NMR). We hypothesized that faster NMR would be associated with greater cigarette puff volume and higher levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a carcinogen biomarker.
  
  
  METHODS
  Current smokers (n = 109) smoked one of their preferred brand cigarettes through a smoking topography device and provided specimens for NMR and total NNAL assays.
  
  
  RESULTS
  Faster nicotine metabolizers (third and fourth quartiles versus first quartile) based on the NMR exhibited significantly greater total puff volume and total NNAL; the total puff volume by daily cigarette consumption interaction was a significant predictor of total NNAL level.
  
  
  CONCLUSIONS
  A heritable biomarker of nicotine clearance predicts total cigarette puff volume and total NNAL.
  
  
  CONCLUSIONS
  If validated, the NMR could contribute to smoking risk assessment in epidemiologic studies and potentially in clinical practice.
authors.affiliation: Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104-3309, USA. strasse3@mail.med.upenn.edu
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Strasser
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Angela G
authors.initials: AG
authors.lastname: Pinto
authors.forename: Kathy Z
authors.initials: KZ
authors.lastname: Tang
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
authors.forename: Steve G
authors.initials: SG
authors.lastname: Carmella
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Caryn E
authors.initials: CE
authors.lastname: Lerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003367:Cotinine / Q000031:analogs & derivatives* / Q000097:blood*; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000493:pharmacokinetics*; D009602:Nitrosamines / Q000652:urine*; D011379:Prognosis; D011725:Pyridines / Q000652:urine*; D018570:Risk Assessment; D012907:Smoking / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D011725:Pyridines; C001381:hydroxycotinine; D009538:Nicotine; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; D003367:Cotinine