Genetic polymorphism of urokinase-type plasminogen activator is interacting with plasminogen activator inhibitor-1 to raise risk of cervical neoplasia

J Surg Oncol. 2012 Aug 1;106(2):204-8. doi: 10.1002/jso.23072. Epub 2012 Feb 21.

Abstract

Background and objectives: To evaluate the impact of plasminogen activator (PA) system genes, including urokinase plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in patients with the cervical neoplasia.

Methods: In total, 336 blood samples were collected from healthy women and 136 patients with cervical neoplasia to analyze the gene polymorphisms of representative PA system genes.

Results: There was no significant association between cervical neoplasia cases and gene polymorphisms of uPA, uPAR and PAI-1 genes as well as to the carcinogenesis of cervical if the cervical neoplasia cases were stratified to HSILs and invasive cancer cases. However, we found a mutual interaction between uPA/PAI-1 genes, which women carrying the uPA/PAI-1 CC/4G4G allele had a 1.70-fold higher risk (OR = 1.70; 95% CI 1.04-2.79) of cervical neoplasia compared with those carrying the CC/4G5G allele.

Conclusions: Individuals with uPA/PAI-1 CC/4G5G allele were in high susceptibility for cervical neoplasia. The combined polymorphism of uPA/PAI-1 might diminish the ability of PAI-1 to inhibiting cervical cancer carcinogenesis when PAI-1 alone as the role of inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Odds Ratio
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Urokinase-Type Plasminogen Activator / genetics*
  • Urokinase-Type Plasminogen Activator / metabolism
  • Uterine Cervical Neoplasms / epidemiology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Plasminogen Activator Inhibitor 1
  • Urokinase-Type Plasminogen Activator