Xue Heng-Chuan, Wang Jian-Ming, Xu Biao, Guo Guo-Ping, Hua Zhao-Lai, Zhou Qin, Zhu Zong-Hai, Ma Zhen-Kai, Gao Jie
Department of Thoracic Surgery,People's Hospital of Yangzhong, Yangzhong, Jiangsu, 212200, P. R. China.
Ai Zheng. 2008 Dec;27(12):1256-62.
BACKGROUND & OBJECTIVE: As one of the principal causes of gene inactivation, aberrant hypermethylation in the promoter of cancer-related genes has attracted more and more attention. However, such studies on esophageal cancer are still limited. This study was to investigate the association between aberrant hypermethylation of MGMT gene and clinical characteristics as well as MTHFR C677T genetic polymorphisms in esophageal squamous cell carcinoma in a Chinese population.
A molecular epidemiologic study was conducted at Yangzhong County, Jiangsu Province of China, on histologically confirmed esophageal squamous cell carcinoma patients who were operated in the People's Hospital of Yangzhong County between January 2005 and March 2006. Peripheral blood samples, esophageal cancer tissues and paracancerous normal tissues were collected. Methylation-specific polymerase chain reaction(MSP) was used to detect the CpG island methylation status of MGMT gene. Restrictive fragment length polymorphism (RFLP) technique was used to test polymorphisms of folate metabolism enzyme gene MTHFR. The association between methylation status of MGMT gene and clinical characteristics as well as MTHFR C677T polymorphisms were analyzed.
Among 125 esophageal squamous cell carcinoma patients, the aberrant hypermethylation rate of MGMT gene was 27.2% in cancer tissues and 11.2% in paracancerous normal tissues. No hypermethylation was found in normal esophageal tissues from 10 healthy adult subjects. Methylation rate of MGMT gene in cancer tissues was significantly higher in the patients with lymph node metastasis than in those without lymph node metastasis (37.3% vs. 18.2%, P=0.017). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol drinking and green tea drinking. After adjusting by potential confounders, variant allele of MTHFR C677T was found to be associated with hypermethylation of MGMT gene. Compared with wild type CC, the odds ratio was 3.34 (95% CI: 1.07-10.39) for CT and 3.83 (95% CI: 1.13-12.94) for TT.
Aberrant CpG island hypermethylation of MGMT gene is closely related with the genesis and progression of esophageal squamous cell carcinoma.
作为基因失活的主要原因之一，癌症相关基因启动子区异常的高甲基化越来越受到关注。然而，食管癌方面的此类研究仍很有限。本研究旨在探讨中国人群食管鳞状细胞癌中MGMT基因异常高甲基化与临床特征以及亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性之间的关系。
在中国江苏省扬中县开展一项分子流行病学研究，研究对象为2005年1月至2006年3月间在扬中县人民医院接受手术治疗、经组织学确诊的食管鳞状细胞癌患者。采集外周血样本、食管癌组织及癌旁正常组织。采用甲基化特异性聚合酶链反应（MSP）检测MGMT基因的CpG岛甲基化状态。采用限制性片段长度多态性（RFLP）技术检测叶酸代谢酶基因MTHFR的多态性。分析MGMT基因甲基化状态与临床特征以及MTHFR C677T多态性之间的关联。
125例食管鳞状细胞癌患者中，癌组织中MGMT基因的异常高甲基化率为27.2%，癌旁正常组织中为11.2%。10例健康成人的正常食管组织中未发现高甲基化现象。有淋巴结转移患者的癌组织中MGMT基因甲基化率显著高于无淋巴结转移者（37.3% 对18.2%，P = 0.017）。未发现异常DNA甲基化与性别、年龄、吸烟、饮酒及饮用绿茶等选定因素之间存在关联。在对潜在混杂因素进行校正后，发现MTHFR C677T的变异等位基因与MGMT基因的高甲基化有关。与野生型CC相比，CT型的比值比为3.34（95%可信区间：1.07 - 10.39），TT型为3.83（95%可信区间：1.13 - 12.94）。
MGMT基因的异常CpG岛高甲基化与食管鳞状细胞癌的发生和进展密切相关。
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