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Journal of Occupational Medicine and Toxicology

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Open Access 01-12-2014 | Short report

Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor gene p16

Authors: Guangming Lu, Huiwen Xu, De Chang, Zhenglai Wu, Xiaoyuan Yao, Shiying Zhang, Zhenlong Li, Jieben Bai, Qing Cai, Wen Zhang

Published in: Journal of Occupational Medicine and Toxicology | Issue 1/2014

Abstract

Background

Occupational and environmental exposure to inorganic arsenic leads to development of cancer and represents a significant health hazard in more than 70 countries. The underlying mechanism for arsenic-induced carcinogenesis remains unclear. Laboratory studies suggest that arsenic is a poor mutagen but may cause epigenetic silencing of key tumor suppressor genes such as p16 through DNA hypermethylation. However, the evidence for an association between human arsenic exposure and abnormal DNA methylation of tumor suppressor genes is lacking.

Findings

Paired case–control studies were conducted involving 40 individuals with high arsenic exposure and arsenicosis, 40 individuals with similarly high exposure to arsenic but without arsenicosis, and 40 individuals with normal exposure to arsenic. DNA methylation status of p16 was determined using methylation-specific PCR. Conditional logistic regression analysis showed that DNA hypermethylation of p16 gene was significantly associated with high arsenic exposure (Odds Ratio = 10.0, P = 0.0019) independently of the development of arsenicosis (Odds Ratio = 2.0, P = 0.1343).

Conclusions

High exposure of arsenic in human is positively linked to DNA hypermethylation of p16 gene, suggesting that epigenetic silencing of key tumor suppressor may be an important mechanism by which arsenic promotes cancer initiation.

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Title: Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor gene p16
Authors: Guangming Lu
Huiwen Xu
De Chang
Zhenglai Wu
Xiaoyuan Yao
Shiying Zhang
Zhenlong Li
Jieben Bai
Qing Cai
Wen Zhang
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Occupational Medicine and Toxicology / Issue 1/2014
Electronic ISSN: 1745-6673
DOI: https://doi.org/10.1186/s12995-014-0042-5

At a glance: The STEP trials

Springer Medicine

Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor gene p16

Abstract

Background

Findings

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Findings

Conclusions

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