Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals

被引:37
作者
Gao, Jianjun [1 ]
Roy, Shantanu [1 ]
Tong, Lin [1 ]
Argos, Maria [1 ]
Jasmine, Farzana [1 ]
Rahaman, Ronald [1 ]
Rakibuz-Zaman, Muhammad [3 ]
Parvez, Faruque [4 ]
Ahmed, Alauddin [3 ]
Hore, Samar K. [5 ]
Sarwar, Golam [3 ]
Slavkovich, Vesna [4 ]
Yunus, Mohammad [5 ]
Rahman, Mahfuzar [3 ]
Baron, John A. [6 ]
Graziano, Joseph H. [4 ]
Ahsan, Habibul [1 ,2 ,7 ,8 ]
Pierce, Brandon L. [1 ,2 ]
机构
[1] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA
[2] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA
[3] UChicago Res Bangladesh, Dhaka, Bangladesh
[4] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA
[5] Int Ctr Diarrheal Dis Res, Dhaka, Bangladesh
[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA
[7] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[8] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
关键词
GENOME-WIDE ASSOCIATION; DRINKING-WATER; OXIDATIVE STRESS; QUANTITATIVE PCR; DNA; CANCER; RISK; BLADDER; LOCUS; BLOOD;
D O I
10.1016/j.envres.2014.09.040
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 possitively 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. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:462 / 469
页数:8
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