癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (4): 255-260.doi: 10.3969/j.issn.1004-616x.2010.04.002

• 论著 • 上一篇    下一篇

转化生长因子β1基因T869C、G915C和C788T多态性与贲门腺癌发病风险的关系

郭炜;单保恩;张超;刘盼;董玉然;郭艳丽;邝钢;董稚明   

  1. 河北医科大学第四医院肿瘤研究所，河北 石家庄 050011
  • 收稿日期:2010-02-23 修回日期:2010-05-10 出版日期:2010-07-30 发布日期:2010-07-30
  • 通讯作者: 单保恩

Correlation of TGF-β1 T869C, G915C and C788T polymorphisms to the risk of gastric cardia adenocarcinoma

GUO Wei;SHAN Bao-en;ZHANG Chao;LIU Pan;DONG Yu-ran;GUO Yan-li;KUANG Gang;DONG Zhi-ming   

  1. Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Received:2010-02-23 Revised:2010-05-10 Online:2010-07-30 Published:2010-07-30
  • Contact: SHAN Bao-en

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摘要： 目的： 探讨转化生长因子β1 (transforming growth factor β1，TGF-β1) 基因T869C、G915C和C788T单核苷酸多态性与中国北方人群贲门腺癌(gastric cardia adenocarcinoma，GCA)遗传易感性的关系。 方法： 采用PCR-RFLP方法检测214名GCA患者和298名健康对照的 TGF-β1基因T869C、G915C和C788T多态性分布情况，同时采用ELISA方法检测血清TGF-β1水平，对110例GCA患者手术切除的肿瘤组织采用免疫组织化学方法检测TGF-β1蛋白表达。 结果： TGF-β1基因T869C 多态性位点的基因型和等位基因型频率在贲门腺癌组和对照组间的分布差异有统计学意义(P<0.05)，GCA患者组C等位基因型频率(55.8％)显著高于对照组(45.8％)(P<0.01)，C等位基因携带者患贲门腺癌的风险是 T等位基因的1.50倍(经性别、年龄和上消化道肿瘤家族史校正后的OR=1.50，95％CI为1.17(2.11)，与TT基因型相比，携带TC和CC基因型可显著增加GCA的发病风险(校正后的OR分别为1.91和2.18，95％CI分别为1.34～2.41和1.56～2.71)。TGF-β1基因G915C和C788T多态性位点的基因型及等位基因型频率在GCA患者组和对照组之间，其总体分布差异均无统计学意义(P>0.05)。贲门腺癌患者血浆TGF-β1水平显著高于对照组(P<0.01)，携带T869C位点C等位基因的GCA患者血浆TGF-β1水平显著高于非携带者(P<0.05)。贲门腺癌组织中TGF-β1蛋白阳性表达率(65.5％)显著高于癌旁组织(15.5％)(P<0.01)，携带T869C位点C等位基因的GCA患者TGF-β1蛋白阳性表达率高于非携带者(P<0.05)。 结论： TGF-β1 T869C位点C等位基因可能是我国北方人群贲门腺癌的遗传易感基因，携带C等位基因的个体可能通过促进TGF-β1的高度表达进而增加了贲门腺癌的发病风险。

关键词: 转化生长因子β1, 单核苷酸多态性, 贲门腺癌, 肿瘤易感性

Abstract: OBJECTIVE: To investigate the possible association of the transforming growth factor β1(TGF-β1) gene T869C, G915C and C788T polymorphisms with susceptibility to gastric cardia adenocarcinoma(GCA) in a population of North China. METHODS: Polymerase-chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to detect the genotype of T869C, G915C and C788T single nucleotide polymorphisms(SNPs) in 214 GCA patients and 298 healthy controls. The level of TGF-β1 was measured by ELISA and the protein expression of TGF-β1 in tumors and corresponding normal tissues was detected by immunohistochemistry method. RESULTS: The overall genotype and allelotype distributions of TGF-β1 T869C polymorphism in GCA patients were significantly different from that in healthy controls(P<0.05). The frequency of C allelotype was significantly higher in GCA patients than that in healthy controls (55.8％ vs.45.8％, P<0.01), the C allelotype significantly increased the risk of developing GCA [adjusted odds ratio (OR)=1.50, 95％ confidence interval(CI)=1.17－2.11]. Compared with TT genotype, the TC and CC genotypes significantly enhanced the risk of developing GCA(adjusted OR=1.91 and 2.18, respectively; 95％CI=1.34－2.41 and 1.56－2.71, respectively). The genotype and allelotype distributions of TGF-β1 G915C and C788T polymorphism in GCApatients were not significantly different from that in healthy controls(P>0.05). The level of TGF-β1 was higher in GCA patients than that in healthy controls(P<0.01) and GCA patients with C allelotype of T869C site were higher than that without C allelotype(P<0.05). The protein expression of TGF-β1 in GCA tumor tissues(65.5％) was significantly higher than that in corresponding normal tissues (15.5％)(P<0.01) and GCA patients with C allelotype of T869C site were higher than that without C allelotype(P<0.05). CONCLUSION: C allelotype of TGF-β1 T869C may be one of the factors that affects the risk of developing GCA in north China and C allelotype carriers may be at increased risk of GCA by enhancing the TGF-β1 expression.

Key words: transforming growth factor β1, polymorphism, gastric cardia adenocarcinoma, susceptibility

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