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

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.