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4G/5G polymorphism in the promoter of plasminogen activator inhibitor-1 (PAI-1) gene in subjects with node-negative and node-positive breast cancer

Beata Smolarz, Janusz Błasiak, Jacek Pytel, Hanna Romanowicz-Makowska, Marek Zadrożny

Med Sci Monit 1999; 5(5): BR833-837 :: ID: 503262

Abstract

PAI-1 is a serine protease inhibitor involved in the degradation of the extracellular matrix during malignant tumor invasion and its high level in breast cancer is associated with a poor prognosis for patients. It is supposed that 4G/5G insertion/deletion polymorphism, with a sequence of either four guanosines or five guanosines, in the promoter of the PAI-1 gene may play a functional role in PAI-1 synthesis, affecting the level of circulating PAI-1. To investigate whether the progression of breast cancer may be related to a particular genotype, 4G/5G polymorphism in patients with node-negative (n=17) and node-positive (n=20) breast cancer was studied. The subjects were 44 to 82 years old, with a median age of 59 years. Formalin-fixed, paraffin-embedded material from ductal breast carcinoma was used. The tumors' diameter was about 20 mm and they were classified of II, II°, III or III°grade. The 4G/5G polymorphism of PAI-1 gene was determined by the allele specific polymerase chain reaction (ASO-PCR). The genotype distribution differed significantly between node-negative and node-positive groups. The 4G allele was observed more frequently in node-negative patients (0.74) compared with 5G allele (0.26), whereas in subjects with node-positive the frequency 4G and 5G allele were 0.48 and 0.52, respectively. Different distribution of the 4G/5G genotypes in patients indicate that this genetic variation itself may be a risk factor for breast cancer invasive phenotype, so the association of the 4G/5G polymorphism with breast cancer progression is worth further studying.

Keywords: PAI-1 - plasminogen activator inhibitor-1, 4G/5G polymorphism, prognostic factor, node-negative and node-positive breast cancer, allele specific polymerase chain reaction (ASO-PCR)

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Medical Science Monitor eISSN: 1643-3750
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