Significance and Status of smad4 Promoter Methylation in the Hans and Kazaks with Esophageal Squamous Cell Carcinoma in Xinjiang
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摘要: 目的 研究新疆汉族与哈族(哈萨克族)食管鳞癌中smad4基因启动子区的甲基化水平及意义。方法 收集哈族食管癌组织37例和正常对照组织33例；汉族食管癌组织31例和正常对照组织33例。应用Mass ARRAY甲基化DNA定量分析技术对食管组织中smad4基因启动子区的甲基化水平行定量分析。结果 汉族与哈族食管癌组和对照组中smad4基因启动子区的平均甲基化率分别为3.4%和2.8%、 3.4%和2.5% ，差异均无统计学意义(P>0.05)。smad4基因启动子区CpG-15、CpG-27 在汉族食管癌中的平均甲基化率(4.7%、4.9%)明显高于对照组 (2.8%、3.5%)；CpG-1、CpG-16-19、CpG-27-28、CpG-31-33在哈族食管癌中的平均甲基化率(1.7%、4.5%、4.9%、6.8%)明显高于哈族对照组(0.7%、2.2%、3.0%、5.5%)，CpG-6在哈族食管癌和正常组织中的平均甲基化水平(1.9%、 1.1%)均明显高于汉族食管癌组(0.4%)，差异均有统计学意义(P<0.05)。结论 (1)smad4基因启动子区的高甲基化可能参与了食管癌的发生。(2)smad4基因启动子区CpG-15、CpG-27的高甲基化可能与汉族食管癌发生关系密切；而CpG-1、CpG-16-19、CpG-27-28、CpG-31-33的高甲基化可能是新疆哈族食管癌高发的原因；smad4 基因启动子区CpG-6的高甲基化可能导致哈族食管癌较汉族食管癌高发。Abstract: Objective To investigate the level and significance of smad4 promoter methylation in the Hans and the Kazaks with esophageal squamous cell carcinoma in Xinjiang. Methods We collected 37 cases of ESCC and 33 cases of local normal esophageal tissues of the Kazaks, and 31 cases of ESCC and 33 cases of local normal esophageal tissues of the Hans. Mass ARRAY methylation DNA quantitative analysis technology was used to detect the methylation status of smad4 gene promoter in ESCC. Results The average methylation rates of smad4 gene promoter CpG units were 3.4% in esophageal cancer in the Hans and 2.8% in relevant control group, 3.4% in esophageal cancer in the Kazaks and 2.5% in relevant control group, with no statistically significant difference (P>0.05). The average methylation rates of CpG-15 and CpG-27(4.7%, 4.9%) in smad4 gene in the Hans with ESCC were significantly higher than those in relevant control group (2.8%, 3.5%). The average methylation rates of CpG-1, CpG-16-19, CpG-27-28, CpG-31-33(1.7%, 4.5%, 4.9%, 6.8%) in smad4 gene in the Kazaks with ESCC were significantly higher than those in relevant control group (0.7%, 2.2%, 3.0%, 5.5%). The average methylation rates of CpG-6 in the Kazaks with ESCC and relevant control group (1.9%, 1.1%) were significantly higher than that in the Hans with ESCC(0.4%), with statistically significant difference (P<0.05). Conclusion Smad4 gene promoter hypermethylation may participate in the occurrence of ESCC. Hypermethylation of CpG-15 and CpG-27 in smad4 gene promoter may closely relate with the occurrence of ESCC in the Hans. Hypermethylation in CpG-1, CpG-16-19, CpG-27-28 and CpG-31-33 may closely relate with the occurrence of ESCC in the Kazaks. Hypermethylation in CpG-6 may result in higher incidence of ESCC in the Kazaks than that in the Hans.
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Key words:
- Esophageal squamous cell carcinoma /
- Smad4 gene /
- Methylation /
- The Kazaks
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