Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism in subjects with cancer

Abstract

Plasminogen activator inhibitor PAI-1 is a fast-acting controlling factor of the plasminogen activator system. The system contains proteolytic enzymes that may contribute to cancer cell invasion by degrading the surrounding extracellular matrix and dissociate cell-cell or cell-matrix attachments. There is substantial evidence in many types of cancer that the antigen content of PAI-1 in primary cancer tissue extracts are of strong prognostic value: high level of PAI-1 in tumor predict poor prognosis for the patient. Moreover, it was demonstrated that the level of PAI-1 in metastasis is significantly higher compared to primary tumors. An insertion/deletion polymorphism in the promoter of the PAI-1 gene has been described that relates to plasma PAI-1 levels. We studied this polymorphism in the plasma of subjects with cancer. Blood was taken from 23 patients (10 breast cancers, 5 gastric cancers, 4 head and neck cancers, 2 melanomas and 2 colorectal cancers) and 23 matched controls. Although frequencies of the 4G and 5G alleles were approximately 0.5/0.5 in both patients and controls, the genotype distribution differed significantly between the two groups – the 4G/5G genotype was observed more frequently in patients with cancer than in the controls. Further studies are needed to check whether the prevalence of the 4G/5G genotype may influence an individual’s plasminogen activation system capacity and thereby contribute in a small way to the cancer risk profile.