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Methylation and expression of tumor-related genes and their associations with folate and MTHFR gene polymorphisms in gastric cancerous tissues

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Author:
No author available
Journal Title:
WORLD CHINESE JOURNAL OF DIGESTOLOGY
Issue:
22
DOI:
10.3969/j.issn.1009-3079.2006.22.008
Key Word:
胃癌;肿瘤相关基因;DNA甲基化;叶酸;MTHFR;基因多态性

Abstract´╝Ü 目的:探讨人胃癌组织中癌基因c-myc,抑癌基因p16INK4A,p21WAF1,错配修复基因hMLH1和hMSH2的甲基化状态及其表达与叶酸、MTHFR基因多态性的关系.方法:胃癌38例手术切除标本的癌区、癌旁和外周正常黏膜组织,运用FOLACS:180自动化学发光系统测定叶酸含量,PCR-RFLP技术检测MTHFR基因677(C→T)和1298(A→C)两个常见多态,并分别以Real-time RT-PCR和甲基化特异性PCR(MSP)技术检测肿瘤相关基因的表达和甲基化状态.结果:C-myc表达升高,p16INK4A,hMLH1和hMSH2表达降低的胃癌黏膜组织其基因启动子区异常甲基化.p21WAFI,hMSH2表达降低,p16INK4A高甲基化者叶酸水平明显降低,c-myc低甲基化和表达升高者中均存在低叶酸水平.MTHFR 677CC基因型的胃癌黏膜组织p16INK4A甲基化升高且表达降低,而其余肿瘤相关基因的甲基化及其表达与MTHFR两个常见多态均无明显相关性.结论:DNA甲基化在胃癌的发生、发展中具有重要作用,叶酸水平和MTHFR基因多态性通过影响部分肿瘤相关基因的甲基化状态而调控其表达.

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