TBX-21基因启动子区多态性与食管鳞癌易感及临床病理特征的相关性研究

Correlation between TBX-21 gene promoter polymorphisms and the risk of esophageal squamous cell carcinoma

目的探讨中国汉族人群中肿瘤免疫调节基因TBX-21启动子区单核苷酸多态性与食管鳞癌的遗传易感及临床病理特征的关联性。方法提取257例食管鳞癌患者及281例健康者外周血基因组DNA,采用PCR-RFLP法检测两组人群TBX-21基因启动子区-1499、-1514两个多态性位点的基因型;以非条件Logistic回归校正混杂因素,并进行多态性与食管鳞癌患者风险的关联分析,以及与食管鳞癌临床病理学特征的相关性分析。结果通过校正性别、年龄、吸烟、饮酒、肿瘤家族史等因素后,Logistic回归分析显示,-1499 G/A位点多态性基因型频率在食管鳞癌组较健康对照组高,具有显著性差异(GA:P=0.009,OR=1.87,95%CI:1.17～2.99;AA:P=0.006,OR=3.12,95%CI:1.39～7.02);而-1514 T/C位点在两组间无显著性差异。与食管鳞癌临床病理学的相关性分析显示,TBX-21基因启动区-1514 T/C多态性与食管鳞癌的侵袭性特征明显相关,其中与淋巴结转移状态有相关性(P=0.025,OR=2.36,95%CI:1.11～5.01),与远处转移的相关性更好(P=0.006,OR=2.44,95%CI:1.30～4.60)。结论 TBX-21基因启动子区-1499 G/A多态性增加了中国汉族人群食管鳞癌的易感风险,而-1514 T/C多态性的改变与食管鳞癌患者的淋巴结及远处转移密切相关。

Objective This study was performed to elucidate whether the polymorphisms within the tumor immunity-regulated gene TBX-21 promoter region were associated with the risk of esophageal squamous cell carcinoma（ESCC） and clinic-pathological characteristics in the Han ethnic group of China.Methods Peripheral blood genomic DNA of 257 patients with ESCC and 281 healthy volunteers were extracted.Two polymorphism genotypes of-1499 and-1514 located in the TBX-21 promoter region were identified by the PCR-restriction fragment length polymorphism（PCR-RFLP） method.Unconditional Logistic regression model adjusted by the confounding factors was used to analyze the correlation between the polymorphism genotypes and the risk of ESCC,and clinic-pathological characteristics.Results By adjusting sex,age,smoking,drinking,family history of cancer,logistic regression analysis revealed a significant higher-1499G/A polymorphism genotype frequencies in ESCC patients compared to control subjects（GA：P=0.009,OR=1.87,95%CI： 1.17-2.99;AA：P=0.006,OR=3.12,95%CI：1.39-7.02）.But-1514T/C polymorphism genotype frequencies between the two groups were no significant differences.TBX-21 gene promoter region-1514T/C polymorphisms genotype frequencies were significantly related to the invasive characteristics of ESCC（lymph node metastasis：P=0.025,OR=2.36,95% CI： 1.11-5.01;distant metastasis： P=0.006,OR=2.44,95% CI： 1.30-4.60）.Conclusion TBX-21 gene promoter region-1499G/A polymorphism in Chinese Han population increases susceptibility to ESCC risk and the changes of-1514T/C polymorphism are closely related to lymph node and distant metastasis.