Wang JianMing, Sasco Annie J, Fu ChaoWei, Xue HengChuan, Guo GuoPing, Hua ZhaoLai, Zhou Qing, Jiang QingWu, Xu Biao
Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Road, Shanghai, China.
Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):118-25. doi: 10.1158/1055-9965.EPI-07-0733.
To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiologic study in China. One hundred and twenty-five histologically confirmed ESCC patients having undergone surgery in the Yangzhong People's Hospital between January 2005 and March 2006 were recruited. The aberrant CpG island hypermethylation of P16, MGMT, and hMLH1 genes could be found in cancer tissues with frequency of about 88.0%, 27.2%, and 3.2%, respectively, and in remote normal-appearing esophageal tissues with frequency of about 36.8%, 11.2%, and 0.0%, respectively. No hypermethylation was found in the normal esophageal tissues from healthy controls. Compared with those patients without lymph node metastasis, MGMT gene showed a higher proportion of hypermethylation in cancer tissues, whereas P16 gene showed a higher proportion of hypermethylation in remote normal-appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues, with odds ratio of 3.34 (95% confidence interval, 1.07-10.39) and 3.83 (95% confidence interval, 1.13-12.94), respectively. This study indicated that the aberrant CpG island hypermethylation of cancer-related genes was associated with ESCC and might be a promising biomarker in diagnosis and prognosis.
为探讨癌症相关基因如P16、MGMT和hMLH1的异常高甲基化在食管鳞状细胞癌（ESCC）中的作用及其与膳食叶酸摄入量和亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性的关系，我们在中国开展了一项分子流行病学研究。招募了2005年1月至2006年3月期间在扬中市人民医院接受手术的125例经组织学确诊的ESCC患者。P16、MGMT和hMLH1基因的异常CpG岛高甲基化在癌组织中的发生率分别约为88.0%、27.2%和3.2%，在距离肿瘤较远的外观正常的食管组织中的发生率分别约为36.8%、11.2%和0.0%。在健康对照的正常食管组织中未发现高甲基化。与无淋巴结转移的患者相比，MGMT基因在癌组织中的高甲基化比例更高，而P16基因在有淋巴结转移患者的距离肿瘤较远的外观正常的食管组织中的高甲基化比例更高。发现MTHFR C677T基因多态性与MGMT基因的CpG岛甲基化状态之间存在显著关联。在对潜在混杂因素进行调整后，携带CT或TT基因型的个体在癌组织中MGMT基因高甲基化的频率更高，优势比分别为3.34（95%置信区间，1.07 - 10.39）和3.83（95%置信区间，1.13 - 12.94）。本研究表明，癌症相关基因的异常CpG岛高甲基化与ESCC相关，可能是诊断和预后中有前景的生物标志物。
