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

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

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.

MeSH terms

  • Case-Control Studies
  • Endometrial Neoplasms / epidemiology*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Logistic Models
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Receptors, Urokinase Plasminogen Activator / genetics*
  • Taiwan / epidemiology
  • Urokinase-Type Plasminogen Activator / genetics*

Substances

  • Plasminogen Activator Inhibitor 1
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator