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

Abstract

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. 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. 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. 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.