title: Association of secondhand smoke exposures with DNA methylation in bladder carcinomas.
abstract: BACKGROUND
  The association between secondhand smoke (SHS) exposure and bladder cancer is inconclusive. Epigenetic alterations in bladder tumors have been linked to primary cigarette smoking and could add to the biological plausibility of an association between SHS exposure and bladder cancer.
  
  
  OBJECTIVE
  SHS exposure is associated with DNA methylation in bladder tumors.
  
  
  METHODS
  Using an array-based approach, we profiled DNA methylation from never smoking cases of incident bladder cancer. Analyses examined associations between individual loci's methylation with SHS variables (exposure in adulthood, childhood, occupationally, and total exposure). A canonical pathway analysis was used to find pathways significantly associated with each SHS exposure type.
  
  
  RESULTS
  There is a trend toward increased methylation of numerous CpG loci with increasing exposure to adulthood, occupational, and total SHS. Discrete associations between methylation extent of several CpG loci and SHS exposures demonstrated significantly increased methylation of these loci across all types of SHS exposure. CpGs with SHS-related methylation alterations were associated with genes in pathways involved in carcinogenesis, immune modulation, and immune signaling.
  
  
  CONCLUSIONS
  Exposures to SHS in adulthood, childhood, occupationally, and in total are each significantly associated with changes in DNA methylation of several CpG loci in bladder tumors, adding biological plausibility to SHS as a risk factor for bladder cancer.
authors.affiliation: Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA.
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Wilhelm-Benartzi
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D019175:DNA Methylation; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012906:Smoke; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000235:genetics*
chemical_list: D012906:Smoke; D014028:Tobacco Smoke Pollution