title: Smoking initiation is followed by the early acquisition of epigenetic change in cervical epithelium: a longitudinal study.
abstract: BACKGROUND
  To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease.
  
  
  METHODS
  Towards this end, a cohort of women aged 15-19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction.
  
  
  RESULTS
  Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09-12.33; P=0.04).
  
  
  CONCLUSIONS
  Smoking initiation is associated with the appearance of methylated forms of CDKN2A.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham, Birmingham, Edgbaston, B15 2TT, UK.
authors.forename: Y T
authors.initials: YT
authors.lastname: Ma
authors.forename: S I
authors.initials: SI
authors.lastname: Collins
authors.forename: L S
authors.initials: LS
authors.lastname: Young
authors.forename: P G
authors.initials: PG
authors.lastname: Murray
authors.forename: C B J
authors.initials: CB
authors.lastname: Woodman
mesh_terms: D000293:Adolescent; D052685:Alphapapillomavirus; D002584:Cervix Uteri / Q000378:metabolism*; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D011795:Surveys and Questionnaires; D014412:Tumor Virus Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000209:etiology; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000209:etiology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16