title: Aberrant p16 methylation, a possible epigenetic risk factor in familial esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Detection of methylation in the p16 gene, an inhibitor of cyclin D-dependent protein kinase, as a new tumor marker for early detection of esophageal squamous cell carcinoma (ESCC) in DNA derived from blood and serum.
  
  
  METHODS
  A large family with clustering of ESCC was assessed in Khorasan province in northeastern Iran. The family had three histologically proven cases of ESCC in two consecutive generations and several other deceased cases with histories of ESCC. DNA from blood of 28 living family members in three consecutive generations, 30 sporadic ESCC cases (from serum, blood, and tumor tissues), and 30 healthy volunteers (from blood) were examined for the methylation status of p16 promoter using methylation-specific PCR (MSP).
  
  
  RESULTS
  Aberrant p16 promoter methylation was found in 64.3% (n = 28) of ESCC family members and none (n = 30) of our normal volunteers. Five of the 28 family members with esophageal cancer symptoms had negative endoscopy results for ESCC, while four of these members had p16 hypermethylation in their blood. The family members with negative endoscopy and positive p16 promoter methylation are being monitored closely for signs of ESCC development through regular check-ups and chromoendoscopies. In sporadic ESCC in northeastern Iran, 73.3% (n = 30) of tumor tissue samples had p16 hypermethylation. Serum and blood samples from the same patients showed p16 hypermethylation in 26.6% and 43.3% of the samples, respectively.
  
  
  CONCLUSIONS
  Aberrant p16 methylation may be a valuable diagnostic tool as a tumor marker for the early identification of individuals in high risk ESCC families.
authors.affiliation: Division of Human Genetics, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. abbaszadegan@ams.ac.ir
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Abbaszadegan
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Raziee
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghafarzadegan
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Shakeri
authors.forename: Sima
authors.initials: S
authors.lastname: Afsharnezhad
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ghavamnasiry
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor