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首页> 外文期刊>Journal of Surgical Oncology >Aberrant methylation of DNA mismatch repair genes in elderly patients with sporadic gastric carcinoma: A comparison with younger patients.
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Aberrant methylation of DNA mismatch repair genes in elderly patients with sporadic gastric carcinoma: A comparison with younger patients.

机译：老年散发性胃癌患者DNA错配修复基因的异常甲基化：与年轻患者的比较。

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摘要

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.
机译：背景：调控DNA修复基因表达的启动子的超甲基化与胃癌（GC）有关。关于疾病发作年龄与分子谱差异之间的关系知之甚少。方法：两个研究组由100名老年患者和100名年轻患者组成。通过亚硫酸氢盐修饰和甲基化特异性PCR（MSP）比较了四个错配修复基因hMLH1，hMSH2，hMSH3和MGMT的异常DNA甲基化模式。结果：老年人的hMLH1和hMSH3的甲基化频率显着高于年轻的GC患者（分别为P <0.001和P = 0.031）。观察到异常的hMLH1，hMSH3和MGMT甲基化与hMLH1，hMSH3和MGMT蛋白表达的丧失之间存在显着相关性（分别为P <0.001，P = 0.002和P = 0.001）。 hMLH1和hMSH3甲基化异常的发生率随着年龄的增长而显着增加。结论：这些结果提示hMLH1和hMSH3的甲基化与年龄有关，因此可能在老年人胃癌的发生中起重要作用。筛选hMLH1和hMSH3甲基化可能对评估老年GC患者具有临床意义。

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