title: Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor gene p16.
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.
  
  
  RESULTS
  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.
authors.affiliation: Institute of Health Management, Chinese PLA General Hospital, Beijing, 100853 China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Institute for Medical Device Standardization Administration, National Institute for Food and Drug Control, Beijing, 100050 China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, General Hospital of Chinese People's Armed Police Forces, Beijing, 100039 China.
authors.forename: De
authors.lastname: Chang
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Beijing, 100005 China.
authors.forename: Zhenglai
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Environmental Health Monitoring, Chinese Center for Disease Control and Prevention, Beijing, 100021 China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Bameng Hygiene and Epidemic Prevention Station, Inner Mongolia, 015000 China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Hangjinhouqi Hygiene and Epidemic Prevention Station, Inner Mongolia, 015400 China.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Hangjinhouqi Hygiene and Epidemic Prevention Station, Inner Mongolia, 015400 China.
authors.forename: Jieben
authors.initials: J
authors.lastname: Bai
authors.affiliation: Key Laboratory of Molecular Biology, Chinese PLA Air Force General Hospital, Beijing, 100036 China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Key Laboratory of Molecular Biology, Chinese PLA Air Force General Hospital, Beijing, 100036 China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
keywords: Arsenic; Cancer; Case–control study; DNA methylation; p16 gene