Association between Five Common Plasminogen Activator Inhibitor-1 (<i>PAI-1</i>) Gene Polymorphisms and Colorectal Cancer Susceptibility

• Main Authors: Jisu Oh, Hui Jeong An, Jung Oh Kim, Hak Hoon Jun, Woo Ram Kim, Eo Jin Kim, Doyeun Oh, Jong Woo Kim, Nam Keun Kim
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: International Journal of Molecular Sciences
• Subjects: colorectal cancer; <i>PAI-1</i>; polymorphism; susceptibility; miRNA
• Online Access: https://www.mdpi.com/1422-0067/21/12/4334
• ISSN: 1661-6596; 1422-0067

The plasminogen activator inhibitor-1 (<i>PAI-1</i>) is expressed in many cancer cell types and modulates cancer growth, invasion, and angiogenesis. The present study investigated the association between five <i>PAI-1 </i>gene polymorphisms and colorectal cancer (CRC) risk. Five <i>PAI-1 </i>polymorphisms (−844G>A [rs2227631], −675 4G>5G [rs1799889], +43G>A [rs6092], +9785G>A [rs2227694], and +11053T>G [rs7242]) were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay in 459 CRC cases and 416 controls. Increased CRC risk was more frequently associated with <i>PAI-1 </i>−675 5G5G polymorphism than with 4G4G (adjusted odds ratio (AOR) = 1.556; 95% confidence interval (CI): 1.012–2.391; <i>p </i>= 0.04). In contrast, for the <i>PAI-1 </i>+11053 polymorphism, we found a lower risk of CRC with the GG genotype (AOR = 0.620; 95% CI: 0.413–0.932; <i>p </i>= 0.02) than with the TT genotype, as well as for recessive carriers (TT + TG vs. GG, AOR = 0.662; 95% CI: 0.469–0.933; <i>p </i>= 0.02). The +43AA genotype was associated with lower overall survival (OS) than the +43GG genotype. Our results suggest that the <i>PAI-1 </i>genotype plays a role in CRC risk. This is the first study to identify an association between five <i>PAI-1 </i>polymorphisms and CRC incidence worldwide.