Plasminogen activator inhibitor 1 (PAI-1) levels and gene promoter polymorphisms in subjects with colorectal cancer

The high level of plasminogen activator inhibitor 1 (PAI-1) in colorectal c ancer predicts poor prognosis for patients. The insertion (5G)/deletion (4G ) polymorphism (the 4G/5G polymorphism) and G -->A single base substitution (the G/A polymorphism) located at promoter of PAI-1 gene may have function al significance in regulation of its expression. In the present work the le vel of PAI-1, distribution of genotypes and frequency of alleles of the 4G/ 5G and G/A polymorphisms in samples of cancer tissue and normal mucosa as w ell as in blood were investigated. Blood, tumor and normal tissues were obt ained from 40 patients with colorectal cancer. The 4G/5G and G/A polymorphi sm were determined by PCR amplification using the allele specific primers. The PAI-1 level was measured by enzyme linked immunosorbent assay (ELISA). The distribution of the genotypes of both polymorphisms did not differ sign ificantly (p > 0.05) from those predicted by the Hardy-Weinberg distributio n. There were no differences in the genotype distributions and allele frequ encies between blood, normal mucosa samples and cancer tissue. The 4G/5G an d G/A polymorphisms were in linkage disequilibrium, The average level of PA I-1 in tumor samples was significantly (p ( 0.05) higher than in normal tis sue. The results obtained indicate that a higher level of PAI-1 can be asso ciated with colorectal cancer. On the other hand, in colon cancer, the 4G/5 G and G/A polymorphisms are not linked with elevated levels of PAI-I and th erefore may not be used to predict colon cancer prognosis.