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

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

doi:10.1186/s12995-014-0042-5

Abstract

BackgroundOccupational 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.FindingsPaired 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).ConclusionsHigh 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12995-014-0042-5) contains supplementary material, which is available to authorized users.

Highlights

Occupational and environmental exposure to inorganic arsenic leads to development of cancer and represents a significant health hazard in more than 70 countries
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
As an attempt to understand the mechanistic link between arsenic exposure and increased cancer risk, we determined whether high exposure to arsenic in human is associated with altered DNA methylation of p16 gene

Summary

Introduction

Occupational and environmental exposure to inorganic arsenic leads to development of cancer and represents a significant health hazard in more than 70 countries. 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. As an attempt to understand the mechanistic link between arsenic exposure and increased cancer risk, we determined whether high exposure to arsenic in human is associated with altered DNA methylation of p16 gene.

Results

Conclusion