Matrix metalloproteinase-2 -1306 C>T gene polymorphism is associated with reduced risk of cancer: a meta-analysis.

Shafiul Haque,Naseem Akhter,Mohtashim Lohani,Arif Ali,Raju K Mandal

doi:10.7314/apjcp.2015.16.3.889

Shafiul Haque, Naseem Akhter + Show 3 more

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https://doi.org/10.7314/apjcp.2015.16.3.889

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Abstract

Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

Highlights

Cancer is a dreadful disease and shown major impact on human health associated with high morbidity and mortality worldwide (Jemal et al, 2011)
Expression of Matrix metalloproteinase-2 (MMP2) is elevated in carcinomas in association with low differentiation grade and accelerated tumor progression (Vihinen and Kahari, 2002)
Having known the important roles of Matrix metalloproteinase (MMPs) in carcinogenesis, it is reasonable to speculate that host genomic polymorphism of MMP2 gene may affect the tumor occurrence

Summary

Introduction

Cancer is a dreadful disease and shown major impact on human health associated with high morbidity and mortality worldwide (Jemal et al, 2011). It is established that cancer is a multistep process, which results from complex interactions between environmental and genetic factors (Pharoah et al, 2000). The precise etiology of this fatal disease is still unclear, it has been suggested that low penetrance gene interplay with environmental factors is a major cause of increasing risk of cancer (Lichtenstein et al, 2000). It is anticipated that the detection of host genetic factors for susceptibility to cancer would significantly help the therapeutic strategies and global control of this deadly disease. MMPs contribute to epithelial-mesenchymal transition, angiogenesis, autophagy, and apoptosis and mainly produced by infiltrating inflammatory cells and stromal cells, which can be stimulated by molecules on the surface of cancer cells (Nabeshima et al, 2002; Deryugina and Quigley, 2006)

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