Aberrant methylation of DNA mismatch repair genes in elderly patients with sporadic gastric carcinoma: A comparison with younger patients.
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.
Kim
Ho Gun
HG
Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju 501-757, Korea.
Lee
Soon
S
Kim
Dong Yi
DY
Ryu
Seong Yeob
SY
Joo
Jae Kyun
JK
Kim
Jung Chul
JC
Lee
Kyung Hwa
KH
Lee
Jae Hyuk
JH
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
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