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. Conclusion: 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. J. Surg. Oncol. 2010;101:28-35. (C) 2009 Wiley-Liss, Inc.