Association Between Genome-Wide Copy Number Variation and Arsenic-Induced Skin Lesions: A Prospective Study

Details

• Personal Author:
  Ahmed A ; Ahsan H ; Argos M ; Graziano JH ; Islam T ; Jasmine F ; Kibriya MG ; Parvez F ; Paul-Brutus R ; Rakibuz-Zaman M ; Roy S ; Shinkle J ; Slavkovich V
• Description:
  Background: Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. Methods: From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. Result: The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. Conclusion: This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions. [Description provided by NIOSH]
• Subjects:
  Arsenic Blood Carcinogens Chemistry Epidemiology Genetics Hematologic Tests Inorganic Chemicals Men Neoplasms Occupational Exposure Occupational Health Risk Assessment Risk Factors Safety Skin Skin Diseases Toxicology Women

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• Keywords:
  Author Keywords: Copy Number Variation Blood Samples Cancer Chemical Properties Chronic Exposure Deoxyribonucleic Acids DNA DNA Damage Drinking Water Gene-environment Interaction Genes Genetic Factors Genetic Predisposition Genomics Genotype Global Health Health Effects Humans LincRNA Longitudinal Study Regression Analysis Ribonucleic Acids Risk Factors RNA Skin Disorders Skin Lesion Skin Lesions Survival Analysis

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• ISSN:
  1476-069X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; Illinois ; Michigan ; New York ; OSHA Region 2 ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  75
• Volume:
  16
• NIOSHTIC Number:
  nn:20051990
• Citation:
  Environ Health 2017 Jul; 16:75
• Contact Point Address:
  Muhammad G. Kibriya, Department of Public Health Sciences, University of Chicago, 900 E 57th Street, KCBD Bldg Room 6110, Chicago, IL 60637, USA
• Email:
  kibriya@uchicago.edu
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Health: A Global Access Science Source
• End Date:
  20290630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2a932eed1075fe4298d0e459bf352a5ebea0a2e0969c62c22a9519a66e7b710d3317ccfa8b11f8f0d1aa0e2066ae47447407b8b2a7f280f284dfdb71a45c6ca8
• Download URL:
  https://stacks.cdc.gov/view/cdc/211628/cdc_211628_DS1.pdf
• File Type:
  [PDF - 750.25 KB ]