Association between Five Common Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms and Colorectal Cancer Susceptibility.

Jisu Oh,Jung Oh Kim,Hui Jeong An,Nam Keun Kim,Jong Woo Kim,Woo Ram Kim,Doyeun Oh,Eo Jin Kim,Hak Hoon Jun

doi:10.3390/ijms21124334

Abstract

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and modulates cancer growth, invasion, and angiogenesis. The present study investigated the association between five PAI-1 gene polymorphisms and colorectal cancer (CRC) risk. Five PAI-1 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 PAI-1 −675 5G5G polymorphism than with 4G4G (adjusted odds ratio (AOR) = 1.556; 95% confidence interval (CI): 1.012–2.391; p = 0.04). In contrast, for the PAI-1 +11053 polymorphism, we found a lower risk of CRC with the GG genotype (AOR = 0.620; 95% CI: 0.413–0.932; p = 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; p = 0.02). The +43AA genotype was associated with lower overall survival (OS) than the +43GG genotype. Our results suggest that the PAI-1 genotype plays a role in CRC risk. This is the first study to identify an association between five PAI-1 polymorphisms and CRC incidence worldwide.

Highlights

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, accounting for >9% of cancer cases
We investigated the effect of five plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms (-675 4G>5G [rs1799889], -844G>A [rs2227631], +43G>A [rs6092], +9785G>A [rs2227694], and +11053T>G [rs7242]) on the risk of CRC in a Korean population-based case-control study
We demonstrated that the plasminogen activator inhibitors (PAIs)-1 -675 4G > 5G and +11053T > G polymorphisms were associated with increased CRC incidence

Summary

Introduction

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, accounting for >9% of cancer cases. Plasminogen activator inhibitor-1 (PAI-1), a 52-kDa glycoprotein belonging to the serine proteinase inhibitor super family, is a multifaceted proteolytic factor located on chromosome 7 (7q21.3–22) It is the principal inhibitor of tissue and urinary plasminogen activators; it constitutes an important regulatory protein in fibrinolysis [9,10]. There is evidence that plasma PAI-1 levels correlate closely with rectal cancer metastasis, and tumor tissue PAI-1 is associated with the histopathology and outcome of rectal cancer [20,21]. We designed a genetic epidemiological study of five PAI-1 polymorphisms (PAI-1 −675 4G > 5G [rs1799889], −844G > A [rs2227631], +43G > A [rs6092], +9785G > A [rs2227694], and +11053T > G [rs7242]) to investigate the association between PAI-1 and CRC. This is the first study to identify an association between five PAI-1 polymorphisms and CRC incidence worldwide

Baseline Characteristics of Colorectal Cancer and Controls

Discussion

Population and Clinical Samples

Polymorphism Analysis

Statistical Analysis