Abstract
Background
Prostate cancer is the second most common cancer in men. Matrix metalloproteinase-2 (MMP2) is the most important member of the matrix metalloproteinase family. MMP2 digests the basement membrane and causes changes in the extracellular matrix which in turn facilitate cancer invasion. It, therefore, has a major role in tumor angiogenesis. Previous studies have identified a single-nucleotide polymorphism C/T at position −1306 of MMP2 gene promoter which is a key regulatory factor in cancer progression.
Aim
The present study aimed to determine the association between MMP2 polymorphism and the risk of prostate cancer in Iranian men.
Methods
This case–control study was performed on 50 paraffin-embedded prostate cancer tissue samples and 54 blood samples from healthy men. Genotyping of the samples was performed using high-resolution melting analysis (HRM). Finally, 20 % of the genotypes were confirmed by sequencing.
Results
No significant associations were found between CT and TT genotypes and the risk of prostate cancer. However, there were no significant relationships between the genotypes and the studied factors, e.g., age, pathological stage, and Gleason Score.
Conclusion
MMP2 −1306 C > T (rs243865) polymorphism was not significantly related with prostate cancer susceptibility in Iranian men.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E et al (2009) Cancer statistics. CA Cancer J Clin 59:225–249
Carter BS, Carter HB, Isaacs JT (1990) Epidemiologic evidence regarding predisposing factors to prostate cancer. Prostate 16:187–197
Bishop JL, Davies A, Ketola K et al (2015) Regulation of tumor cell plasticity by the androgen receptor in prostate cancer. Endoc Relat Cancer 22:165–182
Bookstein R, MacGrogan D, Hilsenbeck SG et al (1993) p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res 53:3369–3373
Björndahl M, Cao R, Nissen LJ et al (2005) Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Proc Natl Acad Sci USA 102:15593–15598
Hojilla CV, Mohammed FF, Khokha R (2003) Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development. Br J Cancer 89:1817–1821
Forget MA, Desrosiers RR, Béliveau R (1999) Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis. Can J Physiol Pharmacol 77:465–480
Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174
Delgado-Enciso I, Cepeda-Lopez FR, Monrroy-Guizar EA et al (2008) Matrix metalloproteinase-2 promoter polymorphism is associated with breast cancer in a Mexican population. Gynecol Obstet Invest 65:68–72
Ozalp S, Tanir HM, Yalcin OT et al (2003) Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors. Eur J Gynaecol Oncol 24:417–420
Price SJ, Greaves DR, Watkins H (2001) Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 276:7549–7558
Ogawa K, Chen F, Kuang C et al (2004) Suppression of matrix metalloproteinase-9 transcription by transforming growth factor-beta is mediated by a nuclear factor-kappaB site. Biochem J 381:413–422
Yu C, Zhou Y, Miao X et al (2004) Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. Cancer Res 64:7622–7628
Chan PK, Chan DP, To KF et al (2001) Evaluation of extraction methods from paraffin wax embedded tissues for PCR amplification of human and viral DNA. J Clin Pathol 54:401–403
Pharoah PD, Dunning AM, Ponder BA et al (2004) Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 4:850–860
Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85
Yoon SO, Park SJ, Yun CH et al (2003) Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J Biochem Mol Biol 36:128–137
Curran S, Murray GI (1999) Matrix metalloproteinases in tumor invasion and metastasis. J Pathol 189:300–308
Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 10:415–433
Sternlicht MD, Werb Z (1999) In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix and adhesion proteins. Oxford University Press, Oxford, UK, pp 503–562
Ye S (2000) Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol 19:623–629
Bian J, Sun Y (1997) Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol 17:6330–6338
Qin H, Sun Y, Benveniste EN (1999) The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 274:29130–29137
Jacobs EJ, Hsing AW, Bain EB et al (2008) Polymorphisms in angiogenesis-related genes and prostate cancer. Cancer Epidemiol Biomarkers Prev 17:972–977
Haque S, Akhter N, Lohani M et al (2015) Matrix Metalloproteinase-2−1306 C > T Gene Polymorphism is Associated with Reduced Risk of Cancer: a Meta-analysis. Asian Pac J Cancer Prev 16:889–896
Liu D, Guo H, Li Y et al (2012) Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis. PLoS One 7:e31251
Peng B, Cao L, Ma X et al (2010) Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk. Mutagenesis 25:371–379
Yaykaşli KO, Kayikçi MA, Yamak N et al (2014) Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer. Turk J Med Sci 44:839–843
Elander N, Söderkvist P, Fransén K (2006) Matrix metalloproteinase (MMP) -1, -2, -3 and -9 promoter polymorphisms in colorectal cancer. Anticancer Res 26:791–795
McColgan P, Sharma P (2009) Polymorphisms of matrix metalloproteinases 1, 2, 3 and 9 and susceptibility to lung, breast and colorectal cancer in over 30,000 subjects. Int J Cancer 125:1473–1478
Kader AK, Shao L, Dinney CP et al (2006) Matrix metalloproteinase polymorphisms and bladder cancer risk. Cancer Res 66:11644–11648
Xu E, Lai M, Lv B et al (2004) A single nucleotide polymorphism in the matrix metalloproteinase-2 promoter is associated with colorectal cancer. Biochem Biophys Res. Commun 324:999–1003
Yu C, Pan K, Xing D et al (2002) Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer. Cancer Res 62:6430–6433
Miao X, Yu C, Tan W et al (2003) A functional polymorphism in the matrix metalloproteinase-2 gene promoter (−1306C/T) is associated with risk of development but not metastasis of gastric cardia adenocarcinomal. Cancer Res 63:3987–3990
Zhou Y, Yu C, Miao X et al (2004) Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes. Carcinogenesis 25:399–404
Grieu F, Li WQ, Iacopetta B (2004) Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype. Breast Cancer Res Treat 88:197–204
Dos Reis ST, Villanova FE, De Andrade PM (2008) Polymorphisms of the matrix metalloproteinases associated with prostate cancer. Mol Med Rep 1:517–520
Dos Reis ST, Villanova FE, Andrade PM (2010) Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer. Urol Oncol 28:624–627
Srivastava P, Lone TA, Kapoor R et al (2012) Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer susceptibility in north India. Arch Med Res 43:117–124
Acknowledgments
The provision of specimens by pathology department of Modarres Hospital (Tehran, Iran) and Kaj laboratory is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare no conflicts of interest.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All ethical considerations are considered in this study. The present case–control study was conducted after obtaining written informed consent from qualified patients interested in participating in the study.
Rights and permissions
About this article
Cite this article
Shajarehpoor Salavati, L., Tafvizi, F. & Manjili, H.K. The association between MMP2 −1306 C > T (rs243865) polymorphism and risk of prostate cancer. Ir J Med Sci 186, 103–111 (2017). https://doi.org/10.1007/s11845-016-1492-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11845-016-1492-9