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P16、MGMT、hMLH1和hMSH2基因的异常DNA甲基化与胃癌中MTHFR C677T基因多态性的联合研究

Aberrant DNA methylation of P16, MGMT, hMLH1 and hMSH2 genes in combination with the MTHFR C677T genetic polymorphism in gastric cancer.

作者信息

Xiong Hai-Lin, Liu Xun-Qi, Sun Ai-Hua, He Ying, Li Jun, Xia Yuan

机构信息

Department of Medical Oncology, Huizhou Municipal Central Hospital, Huizhou, China.

出版信息

Asian Pac J Cancer Prev. 2013;14(5):3139-42. doi: 10.7314/apjcp.2013.14.5.3139.

DOI:10.7314/apjcp.2013.14.5.3139
PMID:23803092
Abstract

Associations of P16, MGMT, hMLH1 and hMLH2 with gastric cancer and their relation with MTHFR status in gastric patients who were confirmed with pathological diagnosis were assessed. Aberrant DNA methylation of P16, MGMT, hMLH1 and hMLH2 and polymorphisms of MTHFR C677T were assayed. The proportional DNA hypermethylation in P16, MGMT, hMLH1 and hMLH2 in cancer tissues was significantly higher than in remote normal-appearing tissues. DNA hypermethylation of P16 and MGMT was correlated with the T and N stages. Individuals with homozygotes (TT) of MTHFR C677T had significant risk of hypermethylation of MGMT in cancer tissues [OR (95% CI)= 3.47(1.41-7.93)]. However, we did not find association between polymorphism in MTHFR C677T and risk of hypermethylation in P16, MGMT, hMLH1 and hMLH2 genes either in cancer or remote normal-appearing tissues. Aberrant hypermethylation of P16, MGMT, hMLH1 and hMLH2 could be predictive of gastric cancer.

摘要

评估了P16、MGMT、hMLH1和hMLH2与胃癌的关联及其与经病理诊断确诊的胃癌患者中MTHFR状态的关系。检测了P16、MGMT、hMLH1和hMLH2的异常DNA甲基化以及MTHFR C677T的多态性。癌组织中P16、MGMT、hMLH1和hMLH2的DNA高甲基化比例显著高于远处外观正常的组织。P16和MGMT的DNA高甲基化与T和N分期相关。MTHFR C677T纯合子(TT)个体在癌组织中MGMT高甲基化的风险显著增加[比值比(95%置信区间)=3.47(1.41 - 7.93)]。然而,无论是在癌组织还是远处外观正常的组织中,我们均未发现MTHFR C677T多态性与P16、MGMT、hMLH1和hMLH2基因高甲基化风险之间存在关联。P16、MGMT、hMLH1和hMLH2的异常高甲基化可能是胃癌的预测指标。

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