title: Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.
abstract: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.
  
  
  
  We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.
  
  
  
  Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff< 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR< 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR< 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR= 0.80).
  
  
  
  OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.
  
  
  
  This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261-9. ©2016 AACR.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York cgh2121@columbia.edu mvg7@cumc.columbia.edu.
authors.forename: Caitlin G
authors.initials: CG
authors.lastname: Howe
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, New York.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, New York.
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Olga
authors.initials: O
authors.lastname: Malysheva
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Lomax-Luu
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York.
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Hasan
authors.initials: H
authors.lastname: Shahriar
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Mohammad N
authors.initials: MN
authors.lastname: Uddin
authors.affiliation: Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.affiliation: Department of Environmental Medicine, NYU Langone Medical Center, New York University, New York.
authors.forename: Max
authors.initials: M
authors.lastname: Costa
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, New York cgh2121@columbia.edu mvg7@cumc.columbia.edu.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000328:Adult; D001151:Arsenic / Q000009:adverse effects*; D001459:Bangladesh / Q000453:epidemiology; D002244:Carbon / Q000378:metabolism*; D003401:Creatine / Q000008:administration & dosage*; D019587:Dietary Supplements; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D042421:Histone Code / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D011499:Protein Processing, Post-Translational / Q000187:drug effects* / Q000235:genetics; D017678:Sex Distribution; D012737:Sex Factors; D014803:Vitamin B Complex / Q000008:administration & dosage; D014874:Water Pollutants, Chemical / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D014874:Water Pollutants, Chemical; D014803:Vitamin B Complex; D002244:Carbon; D005492:Folic Acid; D003401:Creatine; D001151:Arsenic