title: [Hypermethylation and downregulation of tumor suppressor gene p16 in benzene poisoning].
abstract: OBJECTIVE
  To investigate whether benzene negatively affects the expression of p16 through DNA methylation.
  
  
  METHODS
  We carried out a case-control study in Chinese occupational benzene poisoning patients. Eleven cases of BP and 8 controls who were matched for age (+/- 5 years), sex, working duration and job title with BP were recruited. Expression level was examined by quantitative real-time PCR. Bisulfite-PCR pyrosequencing was used to quantitate the level of DNA methylation.
  
  
  RESULTS
  The expression levels of p16 are down-regulated in BP patients compared to the control group (0.53 versus 2.06, P = 0.064). The average percentage of methylated cytosines of p16 was higher in BP group than in controls (12.4%, 11.3%, respectively, P > 0.05). p16 mRNA level decreased with increasing methylation (Pearson r = -0.64, P > 0.05). The fourth CpG site in p16 promoter is located within the consensus binding sequence for olfactory neuron-specific transcription factor. A significant negative correlation between mRNA level and the fourth CpG site was exhibited (Pearson r = - 0.88, P < 0.05).
  
  
  CONCLUSIONS
  Our report demonstrated that mRNA expression of p16 is significantly downregulated in BP patients. Hypermethylation in promoter CpG islands is likely to contribute to the downregulation of p16. Further in-depth studies, utilizing large number of samples, are needed to fully understand the molecular mechanism involved in the tumor-suppressor gene inactivation in benzene-related diseases.
authors.affiliation: National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. caihongxingcn@yahoo.com.cn
authors.forename: Caihong
authors.initials: C
authors.lastname: Xing
authors.forename: Qianfei
authors.initials: Q
authors.lastname: Wang
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Tian
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Yune
authors.initials: Y
authors.lastname: Ni
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Xinbiao
authors.initials: X
authors.lastname: Guo
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
mesh_terms: D000368:Aged; D001554:Benzene / Q000506:poisoning*; D016022:Case-Control Studies; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011041:Poisoning / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D001554:Benzene