caa a22 4500 445315776 CHVBK 20180317142646.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s10552-011-9788-6 doi (NATIONALLICENCE)springer-10.1007/s10552-011-9788-6 Association of secondhand smoke exposures with DNA methylation in bladder carcinomas [Elektronische Daten] [Charlotte Wilhelm-Benartzi, Brock Christensen, Devin Koestler, E. Andres Houseman, Alan Schned, Margaret Karagas, Karl Kelsey, Carmen Marsit] 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. Hypothesis: 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. Interpretation: 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. Springer Science+Business Media B.V., 2011 Bladder cancer nationallicence Secondhand smoking nationallicence DNA methylation nationallicence Methylation profiling nationallicence Array-based methodologies nationallicence Wilhelm-Benartzi Charlotte Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Christensen Brock Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Koestler Devin Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Andres Houseman E. Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Schned Alan Department of Pathology, Dartmouth Medical School, Lebanon, NH, USA aut Karagas Margaret Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA aut Kelsey Karl Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Marsit Carmen Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut Cancer Causes & Control Springer Netherlands 22/8(2011-08-01), 1205-1213 0957-5243 22:8<1205 2011 22 10552 https://doi.org/10.1007/s10552-011-9788-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10552-011-9788-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wilhelm-Benartzi Charlotte Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 700 1- Christensen Brock Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 700 1- Koestler Devin Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 700 1- Andres Houseman E. Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 700 1- Schned Alan Department of Pathology, Dartmouth Medical School, Lebanon, NH, USA aut NATIONALLICENCE 700 1- Karagas Margaret Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA aut NATIONALLICENCE 700 1- Kelsey Karl Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 700 1- Marsit Carmen Department of Community Health Center for Environmental Health and Technology, Brown University, Providence, RI, USA aut NATIONALLICENCE 773 0- Cancer Causes & Control Springer Netherlands 22/8(2011-08-01), 1205-1213 0957-5243 22:8<1205 2011 22 10552 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer