title: Aberrant methylation of DNA mismatch repair genes in elderly patients with sporadic gastric carcinoma: A comparison with younger patients.
abstract: BACKGROUND
  Hypermethylation of promoters that regulate the expression of DNA repair genes is associated with gastric carcinoma (GC). Little is known regarding the association between age of disease onset and differences in molecular profiles.
  
  
  METHODS
  The two study groups consisted of 100 elderly patients and 100 younger patients. The aberrant DNA methylation patterns of four mismatch repair genes, hMLH1, hMSH2, hMSH3, and MGMT, were compared by bisulfite modification and methylation-specific PCR (MSP).
  
  
  RESULTS
  The methylation frequencies for hMLH1 and hMSH3 were significantly higher for the elderly than for the younger GC patients (P < 0.001 and P = 0.031, respectively). A significant correlation was observed between aberrant hMLH1, hMSH3, and MGMT methylation and the loss of hMLH1, hMSH3, and MGMT protein expression (P < 0.001, P = 0.002, and P = 0.001, respectively). The prevalence of aberrant hMLH1 and hMSH3 methylation increased significantly with age.
  
  
  CONCLUSIONS
  These results suggest that the methylation of hMLH1 and hMSH3 is age related and thus may play an important role in gastric carcinogenesis in the elderly. Screening for hMLH1 and hMSH3 methylation may have clinical significance for the evaluation of elderly patients with GC.
authors.affiliation: Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju 501-757, Korea.
authors.forename: Ho Gun
authors.initials: HG
authors.lastname: Kim
authors.forename: Soon
authors.initials: S
authors.lastname: Lee
authors.forename: Dong Yi
authors.initials: DY
authors.lastname: Kim
authors.forename: Seong Yeob
authors.initials: SY
authors.lastname: Ryu
authors.forename: Jae Kyun
authors.initials: JK
authors.lastname: Joo
authors.forename: Jung Chul
authors.initials: JC
authors.lastname: Kim
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000235:genetics; D000074081:MutS Homolog 3 Protein; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein