Kürşat Oğuz YAYKAŞLI, Muhammet Ali KAYIKÇI, Nesibe YAMAK, Hatice SOĞUKTAŞ, Selma DÜZENLİ

Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathological processes such as cancer. In this study, the association between TIMP-2 (-418 G/C) and MMP-2 (-1306 C/T) polymorphisms and prostate cancer in the Turkish population was investigated. Materials and methods: Sixty-one prostate cancer patients and 46 healthy subjects were included in the study. DNA was isolated from 2 mL of peripheral blood taken from subjects, and genotypes were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Results: The TIMP-2 -418 (GC) genotype was found in 15 cases (32.6%) in the control group and in 9 cases (14.8%) in the patients group, and statistical significance was determined (P = 0.037, OR = 0.346). The MMP-2 -1306 (CT) genotype was found 2.17 times more in the patient group than in the control group (P = 0.149, OR = 2.17). Conclusion: Our results show that the TIMP-2 -418 (GC) genotype had a putative protective effect against prostate cancer.

Anahtar Kelimeler:

Matrix metalloproteinases, prostate cancer, polymorphism, tissue inhibitors of metalloproteinases

Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer

Keywords:

Matrix metalloproteinases, prostate cancer, polymorphism, tissue inhibitors of metalloproteinases,

PDF

___

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69–90.
Zhou W, Chen Z, Hu W, Shen M, Zhang X, Li C, Wen Z, Wu X, Hu Y, Zhang X et al. Association of short tandem repeat polymorphism in the promoter of prostate cancer antigen 3 gene with the risk of prostate cancer. PLoS One 2011; 6: e20378.
Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2: 161–74.
Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 2010; 20: 161–8.
Turpeenniemi-Hujanen T. Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie 2005; 87: 287–97.
Turan H, Karkucak M, Yakut T, Ozsahin M, Gurlevik Z, Yanik ME, Ucgun T, Aliagaoglu C, Yaykasli KO. Does MBL2 codon 54 polymorphism play a role in the pathogenesis of psoriasis? Int J Dermatol 2014; 53: 34–8.
Karabulutlu EY, Bilici M, Cayir K, Tekin SB, Kantarci R. Coping, anxiety and depression in Turkish patients with cancer. Eur J Gen Med 2010; 7: 296–302.
Frank SA. Genetic predisposition to cancer - insights from population genetics. Nat Rev Genet 2004; 5: 764–72.
Nakagawa H, Akamatsu S, Takata R, Takahashi A, Kubo M, Nakamura Y. Prostate cancer genomics, biology, and risk assessment through genome-wide association studies. Cancer Sci 2012; 103: 607–13.
Shin YJ, Kim JH. The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells. PLoS One 2012; 7: e30393.
Huang M, Narita S, Tsuchiya N, Ma Z, Numakura K, Obara T, Tsuruta H, Saito M, Inoue T, Horikawa Y et al. Overexpression of Fn14 promotes androgen-independent prostate cancer progression through MMP-9 and correlates with poor treatment outcome. Carcinogenesis 2011; 32: 1589–96.
Nguyen HL, Zucker S, Zarrabi K, Kadam P, Schmidt C, Cao J. Oxidative stress and prostate cancer progression are elicited by membrane-type 1 matrix metalloproteinase. Mol Cancer Res 2011; 9: 1305–18.
Reis ST, Antunes AA, Pontes J Jr, de Sousa-Canavez JM, Dall’Oglio MF, Piantino CB, da Cruz JA, Morais DR, Srougi M, Leite KR. Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer. Int Braz J Urol 2012; 38: 167–74.
Reis ST, Pontes-Junior J, Antunes AA, de Sousa-Canavez JM, Dall’Oglio MF, Passerotti CC, Abe DK, Crippa A, da Cruz JA, Timoszczuk LM et al. MMP-9 overexpression due to TIMP- 1 and RECK underexpression is associated with prognosis in prostate cancer. Int J Biol Markers 2011; 26: 255–61.
Xiao LJ, Lin P, Lin F, Liu X, Qin W, Zou HF, Guo L, Liu W, Wang SJ, Yu XG. ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. Int J Oncol 2012; 40: 1714–24.
Murray NP, Reyes E, Tapia P, Badínez L, Orellana N. Differential expression of matrix metalloproteinase-2 expression in disseminated tumor cells and micrometastasis in bone marrow of patients with nonmetastatic and metastatic prostate cancer: theoretical considerations and clinical implications-an immunocytochemical study. Bone Marrow Res 2012; 2012: 259351.
Oncel M. Matrix metalloproteinases and cancer. Eur J Basic Med Sci 2012; 2: 91–100.
Park KS, Kim SJ, Kim KH, Kim JC. Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol 2011; 26: 391–7.
Alakus H, Afriani N, Warnecke-Eberz U, Bollschweiler E, Fetzner U, Drebber U, Metzger R, Hölscher AH, Mönig SP. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. World J Surg 2010; 34: 2853–9.
Kubben FJ, Sier CF, Meijer MJ, van den Berg M, van der Reijden JJ, Griffioen G, van de Velde CJ, Lamers CB, Verspaget HW. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer 2006; 95: 744–51.
O-Charoenrat P, Khantapura P. The role of genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes in head and neck cancer. Oral Oncol 2006; 42: 257–67.
Bayramoglu A, Gunes HV, Metintas M, Değirmenci I, Mutlu F, Alataş F. The association of MMP-9 enzyme activity, MMP- 9 C1562T polymorphism, and MMP-2 and -9 and TIMP-1, -2, -3, and -4 gene expression in lung cancer. Genet Test Mol Biomarkers 2009; 13: 671–8.
Li XL, Kang S, Zhao XW, Zhang XJ, Zhou RM, Wang N, Jia JH, Zhao J, Li Y. Association of SNPs in the promoter of MMP- 2 and TIMP-2 genes with epithelial ovarian cancer. Yi Chuan 2008; 30: 455–62.
Diao LP, Ma H, Wei GC, Li T, Liu HS, Liu LH, Wu LL, Zhao GM, Gao YH. Matrix metalloproteinase-2 promoter and tissue inhibitor of metalloproteinase-2 gene polymorphisms in non- Hodgkin’s lymphoma. Int J Cancer 2012; 131: 1095–103.
Srivastava P, Lone TA, Kapoor R, Mittal RD. Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer susceptibility in North India. Arch Med Res 2012; 43: 117–24.