title: Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh.
abstract: BACKGROUND
  Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied.
  
  
  METHODS
  We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30-63 years).
  
  
  RESULTS
  Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (P for interaction < 0.10).
  
  
  CONCLUSIONS
  In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys.
  
  
  CONCLUSIONS
  Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Niedzwiecki
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Alam
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York. mvg7@cumc.columbia.edu.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D001151:Arsenic / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D001459:Bangladesh / Q000453:epidemiology; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D060766:Drinking Water / Q000032:analysis; D004781:Environmental Exposure / Q000009:adverse effects* / Q000706:statistics & numerical data; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D055815:Young Adult
chemical_list: D060766:Drinking Water; D006710:Homocysteine; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D001151:Arsenic