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纤溶酶原激活物抑制剂-1 的遗传多态性与子宫内膜癌风险增加相关。

Genetic polymorphism of the plasminogen activator inhibitor-1 is associated with an increased risk of endometrial cancer.

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

J Surg Oncol. 2011 Dec;104(7):755-9. doi: 10.1002/jso.22035. Epub 2011 Jul 14.

DOI:10.1002/jso.22035
PMID:21761413
Abstract

BACKGROUND AND OBJECTIVES

To investigate the association of uPA system genes, including uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 gene polymorphisms, with risk of endometrial cancer.

METHODS

In the present case control study, we enrolled a total of 134 patients with endometrial cancer confirmed by histopathology and 302 unrelated healthy individuals. Genetic polymorphisms of uPA system genes, including uPA rs4065 C/T SNP, uPAR rs344781 T/C SNP, and PAI-1 rs1799889 4G/5G SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis.

RESULTS

Frequency of PAI-1 rs1799889 4G/4G genotype and 4G allele differed significantly between patients with endometrial cancer (36.6% and 61.6%, respectively) and healthy individuals (25.5% and 52.2%, respectively). Individuals with PAI-1 rs1799889 4G/4G genotype were at higher risk of endometrial cancer (OR = 2.26; 95% CI: 1.20-4.27). Stratification analysis showed individuals with PAI-1 rs1799889 4G/4G genotype were at elevated risk for endometrioid type (OR = 2.49; 95% CI 1.27-4.88), low stage (stages I-II) endometrial cancer (OR = 2.34; 95% CI 1.21-4.52). However, no significant differences in uPA C/T SNP, uPAR T/C SNP genotypes were observed between endometrial carcinoma cases and controls.

CONCLUSIONS

Individuals with PAI-1 rs1799889 4G/4G genotype were at significantly higher risk of endometrial cancer in this study.

摘要

背景与目的

研究尿激酶型纤溶酶原激活物(uPA)系统基因,包括 uPA、uPAR 和纤溶酶原激活物抑制剂-1(PAI-1)基因多态性与子宫内膜癌风险的相关性。

方法

在本病例对照研究中,我们共纳入了 134 例经组织病理学证实的子宫内膜癌患者和 302 名无关的健康个体。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对 uPA 系统基因,包括 uPA rs4065 C/T SNP、uPAR rs344781 T/C SNP 和 PAI-1 rs1799889 4G/5G SNP 的遗传多态性进行了基因分型。

结果

子宫内膜癌患者(分别为 36.6%和 61.6%)与健康个体(分别为 25.5%和 52.2%)的 PAI-1 rs1799889 4G/4G 基因型和 4G 等位基因频率存在显著差异。PAI-1 rs1799889 4G/4G 基因型个体患子宫内膜癌的风险更高(OR=2.26;95%CI:1.20-4.27)。分层分析显示,PAI-1 rs1799889 4G/4G 基因型个体患子宫内膜样型(OR=2.49;95%CI 1.27-4.88)和低分期(Ⅰ-Ⅱ期)子宫内膜癌的风险增加(OR=2.34;95%CI 1.21-4.52)。然而,子宫内膜癌病例与对照组之间 uPA C/T SNP 和 uPAR T/C SNP 基因型无显著差异。

结论

在本研究中,PAI-1 rs1799889 4G/4G 基因型个体患子宫内膜癌的风险显著增加。

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