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Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer

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Abstract

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case–control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR–RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.

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Acknowledgements

This study was performed in partial fulfillment of requirements for an MSc degree in the Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah Iran (M. Kamankash). This study was funded by Kermanshah University of Medical Sciences, Kermanshah, Iran (Grant #96430). The Ethics Committee of Kermanshah University of Medical Sciences, Iran approved the present study (1.Research involving Human Participants 2. Informed consent ethical legal cod KUMS.Rec.1396.136)) (Grant #96430). All participants gave informed written consent for use of their samples and clinical data in research.

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Authors and Affiliations

  1. Regenerative Medicine Research Center (RMRC), Kermanshah University of Medical Sciences, Kermanshah, Iran

    Amir Kiani, Mahmoud-Reza Moradi & Saeed Elahi-Rad

  2. Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Marjan Kamankesh, Asad Vaisi-Raygani, Maryam Tanhapour, Mahdieh Aliyari, Faranak Aghaz, Hadi Mozafari, Nayebali Rezvani & Lida Haghnazari

  3. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Zohreh Rahimi & Fariborz Bahrehmand

  4. Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, 858 Madison Ave, Memphis, TN, 48163, USA

    Tayebeh Pourmotabbed

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Kiani, A., Kamankesh, M., Vaisi-Raygani, A. et al. Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer. Mol Biol Rep 47, 9373–9383 (2020). https://doi.org/10.1007/s11033-020-05968-5

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