title: Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism and folate intake in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake.
  
  
  METHODS
  A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR- restriction fragment-length polymorphism (PCR-RFLP).
  
  
  RESULTS
  The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57).
  
  
  CONCLUSIONS
  Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.
authors.affiliation: Department of Cadre Ward, General Hospital of Chengdu Military Area, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Huang
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Duan
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Xiao
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Jiang
authors.forename: Ru
authors.initials: R
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes