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Matrix metalloproteinase (MMP)-1 and MMP-3 gene variations affect MMP-1 and -3 serum concentration and associates with breast cancer

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Abstract

Matrix metallopeptidases (MMPs) 1 and 3 have been shown to contribute to the initiation, and progression of different cancers, including breast cancer (BC). In this study, we aimed to examine the relations between polymorphisms of MMP1 (rs1799750) and MMP3 (rs632478) and their circulating levels with BC. The polymorphisms were genotyped by PCR-based Restriction Fragment Length Polymorphism (RFLP) and Allele-Specific PCR (AS-PCR) among 100 patients and 100 controls. MMP1 and MMP3 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotype distributions of MMP1 and MMP3 genes showed significant difference between patients and controls. The distribution of 2G/2G, 1G/2G and 1G/1G genotypes for MMP1 was 74%, 2% and 24% in the patients and 38%, 2% and 60% in the controls, respectively (P = 0.0001). For MMP3 the distribution of C/C, A/C and A/A genotypes was 28%, 54% and 18% in patients and 48%, 40% and 12% in controls, respectively (P = 0.01). For MMP1, the 2G/2G genotype was linked with a higher risk of BC when compared with that of the 1G/1G genotype (OR = 4.86; 95% CI = 2.63–8.99; P = 0.0001). For MMP3, in co-dominant model, there was a higher risk of BC in A/A and A/C genotype carriers (A/A: OR = 2.57; 95% CI = 1.08–6.11; P = 0.03) (A/C: OR = 2.31 95% CI = 1.24–4.30; P = 0.008). We also showed that MMP1 and MMP3 serum level was significantly increased in BC patients compared to controls. MMP1 and MMP3 genetic variations and their circulating levels are both significantly related to BC.

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Acknowledgements

The authors would like to thank Jam laboratory, sample donors and all the field workers, who supported this study. This study was supported by the University of Guilan and Islamic Azad University of Rasht.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran

    Sahar Balkhi & Ali Salehzadeh

  2. Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran

    Farhad Mashayekhi

  3. Department of Radiation Oncology, Cancer Research Center, Guilan University of Medical Sciences (GUMS), Rasht, Iran

    Hamid Saeedi Saedi

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  1. Sahar Balkhi
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  2. Farhad Mashayekhi
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  3. Ali Salehzadeh
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  4. Hamid Saeedi Saedi
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Contributions

Conceptualization: FM, methodology: FM, formal analysis: SB, investigation: SB, resources: FM and SB, data curation: FM, writing—original draft preparation: SB, visualization: FM, AS and HSS, supervision, FM, AS and HSS.

Corresponding author

Correspondence to Farhad Mashayekhi.

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The authors report no conflict of interest.

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This study was accepted by the University of Guilan ethics committee and has been done in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki).

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All sample donors consented to participate in this investigation.

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Balkhi, S., Mashayekhi, F., Salehzadeh, A. et al. Matrix metalloproteinase (MMP)-1 and MMP-3 gene variations affect MMP-1 and -3 serum concentration and associates with breast cancer. Mol Biol Rep 47, 9637–9644 (2020). https://doi.org/10.1007/s11033-020-05962-x

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