title: Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals.
abstract: BACKGROUND
  Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water.
  
  
  METHODS
  We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1799 individuals. Association between arsenic exposure and a qPCR-based telomere length measure was assessed among 167 individuals.
  
  
  RESULTS
  Urinary arsenic was positively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P<0.00035, Bonferroni-corrected threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction =0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02).
  
  
  CONCLUSIONS
  Our findings suggest that arsenic's carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes.
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Argos
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Rahaman
authors.affiliation: UChicago Research Bangladesh, Dhaka, Bangladesh.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.affiliation: UChicago Research Bangladesh, Dhaka, Bangladesh.
authors.forename: Alauddin
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: Samar K
authors.initials: SK
authors.lastname: Hore
authors.affiliation: UChicago Research Bangladesh, Dhaka, Bangladesh.
authors.forename: Golam
authors.initials: G
authors.lastname: Sarwar
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.affiliation: International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Yunus
authors.affiliation: UChicago Research Bangladesh, Dhaka, Bangladesh.
authors.forename: Mahfuzar
authors.initials: M
authors.lastname: Rahman
authors.affiliation: University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27514, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA; Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA; Departments of Medicine and Human Genetics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA; Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA. Electronic address: brandonpierce@uchicago.edu.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Pierce
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D001459:Bangladesh; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016615:Telomere
chemical_list: D001151:Arsenic