Jianjun Gao1, Shantanu Roy1, Lin Tong1, Maria Argos1, Farzana Jasmine1, Ronald Rahaman1, Muhammad Rakibuz-Zaman2, Faruque Parvez3, Alauddin Ahmed2, Samar K Hore4, Golam Sarwar2, Vesna Slavkovich3, Mohammad Yunus4, Mahfuzar Rahman2, John A Baron5, Joseph H Graziano3, Habibul Ahsan6, Brandon L Pierce7. 1. Department of Public Health Sciences, The University of Chicago, Chicago, IL 60637, USA. 2. UChicago Research Bangladesh, Dhaka, Bangladesh. 3. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. 4. International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh. 5. University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27514, USA. 6. 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. 7. 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.
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). DISCUSSION: 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.
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). DISCUSSION: 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.
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