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Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Purpose

Matrix metalloproteinases play a crucial role in the cancer invasion and metastasis, angiogenesis and tumorigenicity. A single guanine insertion – the 1G/2G polymorphism in the promoter of the matrix metalloproteinase 1 (MMP-1) gene creates a binding site for the transcription factor AP-1 and thus may affect the transcription level of MMP-1. The C→T substitution at the polymorphic site of the MMP-9 gene promoter results in a higher transcription activity of the T-allelic promoter trough the loss of binding site for a repressor protein. The aim of this work was to investigate the influence of 1G/2G and C→T polymorphisms on the MMP-1 and MMP-9 level and therefore on the occurrence and progression of breast cancer.

Experimental design

We investigated the distribution of genotypes and frequency of alleles of the 1G/2G and C→T polymorphisms for 270 patients with breast cancer and 300 healthy women served as control. The genotypes were determined by RFLP-PCR. Additionally, we estimated the level of MMP-1 and MMP-9 antigens in tumor samples and normal breast tissue using ELISA.

Results

The levels of MMP-1 in tumor samples of node positive patients ware significantly higher than in samples of node negative patients (p<0.05). Increased level of MMP-9 correlates with Bloom-Richardson grading III (p<0.05), increased tumor size (p<0.05) and absence of estrogen and progesterone receptors (p<0.01). Additionally, both MMP-1 and MMP-9 levels were higher in tumor than in the normal breast tissue. We showed the higher risk of metastasis development in lymph node for the 2G/2G genotype (OR=2.14; CI 95% 1.24;3.69) and the 2G allele carriers (OR=1.68; CI 95% 1.19;2.39). We found correlation between the T allele (OR=2.61; CI 95% 1.33;4.87), 2G (OR=2.58; CI 95% 1.35;4.91) and malignance.

Conclusion

The results suggest that MMP-1 is responsible for the local invasion and MMP-9 is associated with the malignance and the growth of the tumor. We suggest that the 2G allele of the 1G/2G MMP-1 gene polymorphism may be associated with the lymph node metastasis in patients with breast cancer and therefore it can be considered as a progression marker in this disease.

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Acknowledgements

This work was supported by the grants 6P05A 045 21 from KBN (KP) and 505/363 from University of Lodz (JB).

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Authors and Affiliations

  1. Department of Molecular Genetics, University of Lodz, Lodz, Poland

    Karolina Przybylowska, Anita Kluczna & Janusz Blasiak

  2. Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland

    Marek Zadrozny, Tadeusz Krawczyk & Andrzej Kulig

  3. Department of Surgical Oncology, N. Copernicus Memorial Hospital, Lodz, Poland

    Jan Rykala, Agnieszka Kolacinska & Zbigniew Morawiec

  4. Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland

    Jozef Drzewoski

Authors
  1. Karolina Przybylowska
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  2. Anita Kluczna
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Address for offprints and correspondence: Janusz Blasiak, Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland; Tel.: +48-42-635-44-89; Fax: +48-42-635-44-84; E-mail: januszb@biol.uni.lodz.pl

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Przybylowska, K., Kluczna, A., Zadrozny, M. et al. Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Res Treat 95, 65–72 (2006). https://doi.org/10.1007/s10549-005-9042-6

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  • DOI: https://doi.org/10.1007/s10549-005-9042-6

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