Cancer Causes & Control

, Volume 22, Issue 8, pp 1205–1213

Association of secondhand smoke exposures with DNA methylation in bladder carcinomas

  • Charlotte S. Wilhelm-Benartzi
  • Brock C. Christensen
  • Devin C. Koestler
  • E. Andres Houseman
  • Alan R. Schned
  • Margaret R. Karagas
  • Karl T. Kelsey
  • Carmen J. Marsit
Brief report



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.


SHS exposure is associated with DNA methylation in bladder tumors.


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.


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.


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.


Bladder cancer Secondhand smoking DNA methylation Methylation profiling Array-based methodologies 

Supplementary material

10552_2011_9788_MOESM1_ESM.doc (237 kb)
Supplementary material 1 (DOC 237 kb)


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Charlotte S. Wilhelm-Benartzi
    • 1
  • Brock C. Christensen
    • 1
    • 2
  • Devin C. Koestler
    • 1
  • E. Andres Houseman
    • 1
  • Alan R. Schned
    • 3
  • Margaret R. Karagas
    • 4
  • Karl T. Kelsey
    • 1
    • 2
  • Carmen J. Marsit
    • 1
    • 2
  1. 1.Department of Community Health Center for Environmental Health and TechnologyBrown UniversityProvidenceUSA
  2. 2.Department of Pathology and Laboratory MedicineBrown UniversityProvidenceUSA
  3. 3.Department of PathologyDartmouth Medical SchoolLebanonUSA
  4. 4.Department of Community and Family MedicineDartmouth Medical SchoolLebanonUSA

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