title: DNA methylation as a long-term biomarker of exposure to tobacco smoke.
abstract: BACKGROUND
  Most biomarkers of exposure tend to have short half-lives. This includes cotinine, a metabolite of nicotine widely used to assess smoke exposure. Cotinine is thus unsuitable as a determinant of past exposure to cigarette smoke.
  
  
  METHODS
  We used bisulphite pyrosequencing of a set of four genomic loci (AHRR, 6p21, and two at 2q37) that had differential DNA methylation levels in peripheral blood DNA dependent on tobacco exposure to create a predictive model of smoking status.
  
  
  RESULTS
  Combining four gene loci into a single methylation index provided high positive predictive and sensitivity values for predicting former smoking status in both test (n = 81) and validation (n = 180) sample sets.
  
  
  CONCLUSIONS
  This study provides a direct molecular measure of prior exposure to tobacco that can be performed using the quantitative approach of bisulphite pyrosequencing. Epigenetic changes that are detectable in blood may more generally act as molecular biomarkers for other exposures that are also difficult to quantify in epidemiological studies.
authors.affiliation: Department of Surgery and Cancer, Epigenetics Unit, Imperial College London, London, United Kingdom.
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Shenker
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.forename: Karin
authors.initials: K
authors.lastname: van Veldhoven
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ricceri
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: James M
authors.initials: JM
authors.lastname: Flanagan
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D015415:Biomarkers / Q000097:blood; D003367:Cotinine / Q000097:blood; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D015203:Reproducibility of Results; D012907:Smoking / Q000097:blood* / Q000235:genetics*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003367:Cotinine