Letter to the Editor Controversial role of MMP-9 gene in MS disease To the Editor, We read with interest and pleasure the article by La Russa and colleagues on the association of matrix metalloproteinase-9 gene (MMP-9) gene with multiple sclerosis (MS) in an Italian case–control study (Antonella La Russa et al., 2010). In our opinion, there are some interesting points about the role of the MMP-9 gene in both MS and cancer needed to be further elucidated by future studies. The recent investigation supported by previous studies has shown that a functional variant within the MMP-9 gene (-1562C/T) is significantly associated with MS disease (Antonella La Russa et al., 2010). MMP-9 (gelatinase A and gelatinase B) are known to play a critical role in tumour invasion and metastasis development. The higher expression of MMP-9 has been reported in several cancers (Rollin et al., 2007). Also, several studies have illustrated an increased risk for -1562C/T single nucleotide polymorphism (SNP) in breast cancer (Przybylowska et al., 2006; Hughes et al., 2007; Lei et al., 2007). On the other hand, some surprising investigations have shown no association between MS and cancer, in particular breast cancer (Fois et al., 2010; Lebrun et al., 2008; Handel and Ramagopalan, 2010). So there comes a controversial question: how could it be explained that the MMP-9 gene is strongly linked to both MS and cancer whereas there is no signal of association between these two diseases? Notably, Nelissen et al. (Nelissen et al., 2000) declared no evidence of association for MMP-9 SNP and Benešová et al. (Benešová et al., 2008) indicated a significant decrease of the -1562T allele carriers in MS patients compared to controls. These results are entirely inconsistent with those obtained by La Russa et al. (La Russa et al., 2010) reporting a remarkable frequency of -1562T allele among MS patients. Taken together, it is likely that this gene has a multitude of roles, some of which may contribute to the MS pathogenesis and others to the aetiology of cancer and thus further studies are required to clear this ambiguity. References Benešová, et al., 2008. Matrix metalloproteinase-9 and matrix metalloproteinase-2 gene polymorphisms in multiple sclerosis. J. Neuroimmunol. 205, 105–109. Fois, et al., 2010. Cancer in patients with motor neuron disease, multiple sclerosis and Parkinson's disease: record linkage studies. J. Neurol. Neurosurg. Psychiatry 81, 215–221. Handel, A.E., Ramagopalan, S.V., 2010. Multiple sclerosis and risk of cancer: a meta- analysis. J. Neurol. Neurosurg. Psychiatry. DOI:10.1136/jnnp.2009.195776 [Epub ahead of print]. Hughes, et al., November 15, 2007. Matrix metalloproteinase single-nucleotide polymorphisms and haplotypes predict breast cancer progression. Clin. Cancer Res. 13 (22), 6673. La Russa, Antonella, et al., 2010. Single nucleotide polymorphism in the MMP-9 gene is associated with susceptibility to develop multiple sclerosis in an Italian case– control study. J. Neuroimmunol.10.1016/j.jneuroim.2010.04.016. Lebrun, et al., 2008. Cancer risk and impact of disease-modifying treatments in patients with multiple sclerosis. Mult. Scler. 14, 399–405. Lei, et al., 2007. Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression. Breast Cancer Res. Treat. 103, 61–69. Nelissen, et al., 2000. Polymorphism analysis suggests that the gelatinase B gene is not a susceptibility factor for multiple sclerosis. J. Neuroimmunol. 105, 58–63. Przybylowska, et al., 2006. Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Res. Treat. 95, 65–72. Rollin, et al., 2007. Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer. Lung Cancer 56, 273–280. Hamid Zahednasab Department of Clinical Biochemistry, Faculty of Medicine, University of Tarbiat Modares, Tehran, Iran M. Reza Jabalameli Seyed Amir Bahreini⁎ Department of Molecular Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran ⁎Corresponding author. Department of Molecular Biology, Faculty of Sciences, Hezar Jerib Street, Azadi Plaza, Isfahan, Iran. E-mail address: a.bahraini88@gmail.com (S.A. Bahreini). Mohammad Saadatnia Department of Neurology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Hamid Zarkesh-Esfahani Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Abolghasem Esmaeili Department of Biotechnology, Faculty of New Sciences and Technologies, University of Isfahan, Isfahan, Iran 26 May 2010 Journal of Neuroimmunology 230 (2011) 191 0165-5728/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jneuroim.2010.09.006 Contents lists available at ScienceDirect Journal of Neuroimmunology journal homepage: www.elsevier.com/locate/jneuroim