Skip to main content

Advertisement

Log in

Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin’s lymphoma in Egyptians

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix degradation. MMP2 is the key molecule that control invasion, tumor growth, and metastasis, and has been associated with poor prognosis in several tumors. Several epidemiological studies have focused on the associations between MMP2 promoter polymorphisms and cancer susceptibility; however, little is known about their role in hematological malignancies. The present study aimed to investigate the association of MMP2 −735C/T and −1306C/T promoter polymorphisms with B-NHL susceptibility and their clinicopathological characteristics. The study included 100 B-NHL patients and 100 healthy controls. Genotyping of MMP2 −735C/T and MMP2 −1306C/T was done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. MMP2 −735C/T heteromutant genotype (CT) was detected in 23 % of patients, and the homomutant genotype (TT) was detected in 7 % of patients. The polymorphic allele, T allele, was associated with susceptibility to B-NHL (OR = 2.8:95 %CI = 1.48–5.28). For MMP2 −1306C/T, the frequencies of the polymorphic variants were 5 % for the heteromutant genotype (CT) and 3 % for the homomutant genotype (TT). The polymorphic allele, T allele, conferred almost fourfold increased risk of B-NHL (OR = 3.8, 95 %CI = 1.05–13.9), and the risk elevated to be almost eight folds when confined to diffuse large B-cell lymphoma (DLBCL) (OR = 7.9, 95 %CI = 1.67–32.27). MMP2 −735C/T polymorphic genotypes were correlated with advanced clinical stages of the disease (stages III and IV). In conclusion, the study revealed that the variant alleles of MMP2 −735C/T and MMP2 −1306C/T can be considered as molecular risk factors for B-NHL among Egyptians.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Nogai H, Do¨rken B, Lenz G (2001) Pathogenesis of non-Hodgkin’s lymphoma. J Clin Oncol 29:1–9

    Google Scholar 

  2. Diao LP, Ma H, Wei GC, Li T, Liu HS, Liu LH, Wu LL, Zhao GM, Gao YH (2011) Matrix metalloproteinase-2 promoter and tissue inhibitor of metalloproteinase-2 gene polymorphisms in non-Hodgkin’s lymphoma. Int J Cancer 000:000–000

    Google Scholar 

  3. Skibola CF, Curry JD, Neiters A (2007) A genetic susceptibility to lymphoma. Haematologica 92:960

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42:113–185

    Article  CAS  PubMed  Google Scholar 

  5. Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Cancer Biol 10:415–433

    Article  CAS  Google Scholar 

  6. Price SJ, Greaves DR, Watkins H (2001) Identification of novel, functional geneticvariants in the human matrixmetalloproteinase-2 gene: role of Sp1 inallele-specific transcriptional regulation. J Biol Chem 276:7549–7558

    Article  CAS  PubMed  Google Scholar 

  7. Vasku A, Tschoplova S, Izakovicova Holla L, Semradova V, Vacha J (2002) Genotype association of C(735)T polymorphism inmatrix metalloproteinase 2 gene with G(8002)A endothelin 1 gene with plaque psoriasis. Dermatology 262:204–205

    Google Scholar 

  8. Zhou Y, Yu C, Miao X, Tan W, Liang W, Xiong P, Sun T, Lin D (2004) Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 genes. Carcinogenesis 25:399–404

    Article  CAS  PubMed  Google Scholar 

  9. Shao JY, Cao Y, Niao XP et al (2001) A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China. Chin J Cancer 30:620–626

    Article  Google Scholar 

  10. Peng B, Cao L, Ma X, Wang W, Wang D, Yu L (2010) Meta-analysis of association between matrix metalloproteinasess2, 7 and 9 promoter polymorphisms and cancer risk. Mutagenesis. doi:10.1093/mutage/geg015

    Google Scholar 

  11. Qui W, Zhou G, Zhai Y et al (2008) No association of MMp-7, MMP-8, and MMP-21 polymorphisms in a Chinese population. Cancer Epidemiol Biomarkers Prev 17:2514–2518

    Article  Google Scholar 

  12. Armitage JO (2005) Staging non-Hodgkin lymphoma. CA Cancer J Clin 55:368–376

    Article  PubMed  Google Scholar 

  13. Wróbel T, Mazur G, Dzietczenia J, Gwbura K, Kuliczkowski K, Bogunia-Kubik K (2013) VEGF and bFGF gene polymorphisms in patients with non-Hodgkin’s lymphoma. BioMed Research International Volume 2013, Article ID 159813, 6 pages http://dx.doi.org/10.1155/2013/159813

  14. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839

    Article  CAS  PubMed  Google Scholar 

  15. O-Charoenrat P, Khantapura P (2006) The role of genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2genes in head and neck cancer. Oral Oncol 42:257–267

    Article  CAS  PubMed  Google Scholar 

  16. Negard HF, Svennevig K, Kolset SO, Iversen N, Lothe IM, Ostenstad B, Sandset PM, Iversen PO (2009) Alteration in regulators of the extracellular matrix in non-Hodgkin lymphomas. Leuk Lymphoma 50:998–1004

    Article  Google Scholar 

  17. Vasku A, Vasku J.B, Necas M., Vasku V (2010) Matrix Metalloproteinase-2 promoter genotype as a marker of cutaneous T-cell lymphoma early stage. Journal of Biomedicine and Biotechnology. 5

  18. Mossböck G, Weger M, Faschinger C, Zimmermann C, Schmut O, Renner W, El-Shabrawi Y (2010) Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in open angle glaucomas. Mol Vis 16:1764–1770

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maha Hamdi El Sissy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gouda, H.M., Khorshied, M.M., El Sissy, M.H. et al. Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin’s lymphoma in Egyptians. Ann Hematol 93, 1313–1318 (2014). https://doi.org/10.1007/s00277-014-2054-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-014-2054-8

Keywords

Navigation