转化生长因子β_1基因多态性与食管癌的关系

Correlation between of serum level and genotype of TGF-β_1 in patients with esophageal cancer

目的研究转化生长因子β1(TGF-β1)基因启动子区-800G/A和第1外显子+915G/C基因多态性各等位基因及基因型在食管癌患者中的分布频率,初步分析其基因型及血清水平与食管癌的相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)和聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测118例食管癌患者和130例正常对照组TGF-β1的基因多态性,包括TGF-β1基因启动子-800G/A、第1外显子+915G/C位点,同时采用酶联免疫吸附试验(ELISA)检测血清TGF-β1水平。结果食管癌患者血清TGF-β1水平显著高于对照组(P<0.01),TGF-β1基因-800G/A位点多态性在食管癌组和正常人群中的分布差异无显著性(P>0.05),而TGF-β1基因+915G/C多态性各等位基因及基因型频率在两组人群中的分布差异存在显著性(P<0.05),等位基因频率的相对风险分析发现,C等位基因携带者患食管癌的风险是G等位基因的3.077倍(OR=3.077,95%CI:1.336-7.087),携带C等位基因的食管癌患者血清TGF-β1水平显著高于不携带者(55.37±9.76)μg/L VS(48.29±8.29)μg/L,P<0.05。结论TGF-β1基因+915G/C多态性与食管癌的发病具有相关性,其中C等位基因可能是食管癌发病的遗传易感基因;携带C等位基因的个体可能通过促进TGF-β1的高度表达而增加了食管癌的发病风险。

Objective To study the relationship the allele frequencies and genotype distribution of transforming growth factor-beta 1 （TGF-β1）gene promoter and the exon 1 polymorphisms in Chinese patients with esophageal cancer, and to analyze association the sermn levels and genotype of TGF-β1 with esophageal cancer. Methods The polymorphisms of TGF-β1 gene, including polymorphisms of TGF-β1 gene - 800G/A, ＋ 915G/C, were analyzed by the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and sequence specific primers-polymerase chain reaction（PCR-SSP） methods in 118 patients with esophageal cancer and 130 healthy controls, and the serum level of TGF-β1 was determined by enzyme-linked immunosorbent assay（ ELISA）. Results The esophageal cancer group showed significandy higher serum levels of TGF-β1 than control group（ P 〈 0.01 ）, The distributions of TGF-β1 gene -800G/A polymorphisms were not different between esophageal cancer group and control group, but the TGF-β1 ＋ 915G/ C gene polymorphism was significantly different. The relative risk suffered from esophageal cancer of C allele was 1.624 times of the T allele（OR = 1.624,95%CI： 1. 134 - 2. 324）, the serum level of TGF-β1 T allele carriers was significantly higher than no carriers （50.97±8.91 μg/L VS44.23±8.54 μg/L P〈 0.01）.Conclusion TGF-β1 gene ＋ 915G/C polymorphism was associated with esophageal cancer, and T allele may be a risk factor for esophageal cancer. In which the TGF-β1 T allele carriers may be increase risk by enhancing the TGF-β1 expression in the pathogenesis of esophageal cancer.