title: Epigenetic changes of TIMP-3, GSTP-1 and 14-3-3 sigma genes as indication of status of chronic inflammation and cancer.
abstract: OBJECTIVE
  This study aimed to compare the epigenetic changes via hypermethylation status of TIMP-3, GSTP-1 and 14-3-3σ genes, between healthy subjects and patients with reversible chronic inflammatory disease, and between healthy subjects and patients with irreversible malignant disease, to highlight the genetic changes that occur in the progression from an inflammatory condition to irreversible genetic changes commonly observed in cancer patients.
  
  
  METHODS
  DNA was extracted from the blood of 680 healthy subjects, and tissues and blood of 110 patients with chronic inflammation disease of the gums, as well as neoplastic tissues of 108 breast cancer patients. Methylation-specific polymerase chain reaction (PCR) for TIMP-3, GSTP-1 and 14-3-3σ was performed, and hypermethylation status was analyzed and compared between the 3 groups.
  
  
  RESULTS
  The hypermethylation frequencies of TIMP-3 and GSTP-1 of reversible chronic inflammatory gum disease and the control group were similar, but both were significantly lower than those for malignant disease patients (p<0.0001). The methylation frequency of 14-3-3σ in chronic inflammatory gum disease was higher than in the cancer and control groups (p<0.0001). The methylation of CpG islands in TIMP-3 and GSTP-1 in chronic inflammation patients occurred as frequently as in the control group, but less frequently than in breast cancer patients. However, the epigenetic silencing of 14-3-3σ occurred more frequently in the chronic inflammation group than in cancer patients and healthy controls.
  
  
  CONCLUSIONS
  The epigenetic silencing of 14-3-3σ might be essential for chronic inflammatory gum disease. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to cancer.
authors.affiliation: Department of Stomatology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province - PR China.
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.forename: William W N
authors.initials: WW
authors.lastname: Tsang
authors.forename: Liang
authors.initials: L
authors.lastname: Hao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Louis W C
authors.initials: LW
authors.lastname: Chow
authors.forename: Mary N B
authors.initials: MN
authors.lastname: Cheung
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Elizabeth L Y
authors.initials: EL
authors.lastname: Ng
authors.forename: Wings T Y
authors.initials: WT
authors.lastname: Loo
authors.forename: Christopher Y C
authors.initials: CY
authors.lastname: Chow
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Bai
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002908:Chronic Disease; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D044127:Epigenesis, Genetic; D005095:Exoribonucleases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005891:Gingivitis / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005095:Exoribonucleases; C413442:SFN protein, human