Plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G polymorphism and endometrial cancer. Influence of PAI-1 polymorphism on tissue PAI-1 antigen and mRNA expression and tumor severity

• Published in: Thrombosis research Vol. 130; no. 2; pp. 242 - 247
• Main Authors: Gilabert-Estellés, Juan, Ramón, Luis A, Braza-Boïls, Aitana, Gilabert, Juan, Chirivella, Melitina, España, Francisco, Estellés, Amparo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-08-2012; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium - metabolism; Endometrium - pathology; Female; fibrinolysis; Gene Expression Regulation, Neoplastic; Gene Frequency; Genotype; Hematology, Oncology and Palliative Medicine; Humans; Medical sciences; Middle Aged; PAI-1 4G/5G polymorphism (rs1799889); Plasminogen Activator Inhibitor 1 - genetics; plasminogen activator inhibitor-1 (PAI-1); Polymorphism, Single Nucleotide; RNA, Messenger - genetics; SERPINE1; fibrinolysis; PAI-1 4G/5G polymorphism (rs1799889); Endometrial cancer; plasminogen activator inhibitor-1 (PAI-1); SERPINE1; Endometrium cancer; Cardiovascular disease; Malignant tumor; Fibrinolysis; Female genital diseases; Plasminogen activator inhibitor 1; Uterine diseases; Cancer; Polymorphism
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.10.007

Abstract Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in endometrial cancer patients are associated with a poor prognosis. The objective of this study was to evaluate the PAI-1 4G/5G polymorphism in women with and without endometrial cancer and to analyze the influence of this polymorphism on PAI-1 expression in endometrial tissue. In 423 women (212 patients with endometrial cancer and 211 controls) PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Quantitative real-time RT-PCR assay was used to quantify PAI-1 mRNA and PAI-1 protein levels were quantified by ELISA in tissue extracts from 33 patients with endometrial cancer and from 70 endometrial tissues from control women. The frequency of PAI-1 4G/4G genotype ( P = 0.010) and the PAI-1 4G allele ( P = 0.009) was significantly higher in patients than in controls. The frequency of PAI-1 4G allele was significantly higher in patients with stage IB than in those with stage IA ( P = 0.03). Control women with the 4G/4G genotype had higher endometrial PAI-1 protein ( P = 0.018) and mRNA ( P = 0.004) levels than those with the 5G/5G genotype. A significant increase in PAI-1 protein and mRNA was observed in endometrial cancer tissue in comparison with the endometrial tissue from control women ( P < 0.01). In conclusion, frequencies of the PAI-1 4G allele and 4G/4G genotype were found significantly more often in women with endometrial cancer than in controls. PAI-1 levels in endometrial tissue seem to be associated with PAI-1 4G/5G polymorphism. These findings suggest that the PAI-1 4G/4G genotype may be associated with the risk of endometrial cancer in a Caucasian population. Further studies with a larger number of patients are needed to clarify the influence of this PAI-1 polymorphism in endometrial cancer.