Abstract
Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case–control design the association between the functional −1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case–control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 −1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44–1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40–1.94, P = 0.84). When the MMP-9 −1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 −1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.
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References
Fock KM (2014) Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther 40:250–260
de Martel C, Forman D, Plummer M (2013) Gastric cancer: epidemiology and risk factors. Gastroenterol Clin N Am 42:219–240
Lordick F, Allum W, Carneiro F, Mitry E, Tabernero J, Tan P, Van Cutsem E, van de Velde C, Cervantes A (2014) Unmet needs and challenges in gastric cancer: the way forward. Cancer Treat Rev 40:692–700
Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12:354–362
Shi J, Qu YP, Hou P (2014) Pathogenetic mechanisms in gastric cancer. World J Gastroenterol 20:13804–13819
McLean MH, El-Omar EM (2014) Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 11:664–674
Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R, Kaur G (2014) Matrix metalloproteinases and cancer—roles in threat and therapy. Asian Pac J Cancer Prev 15:1085–1091
Nissinen L, Kähäri VM (2014) Matrix metalloproteinases in inflammation. Biochim Biophys Acta 1840:2571–2580
Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S (2014) Matrix metalloproteinases and gastrointestinal cancers: impacts of dietary antioxidants. World J Biol Chem 5:355–376
Sampieri CL, León-Córdoba K, Remes-Troche JM (2013) Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers. J Cancer Res Ther 9:356–363
Chen J, Chen LJ, Zhou HC, Yang RB, Lu Y, Xia YL, Wu W, Hu LW (2014) Prognostic value of matrix metalloproteinase-9 in gastric cancer: a meta-analysis. Hepatogastroenterology 61:518–524
Zhang QW, Liu L, Chen R, Wei YQ, Li P, Shi HS, Zhao YW (2012) Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis. Asian Pac J Cancer Prev 13:2903–2908
Singh K, Nair RR, Khanna A (2012) Functional SNP -1562C/T in the promoter region of MMP9 and recurrent early pregnancy loss. Reprod Biomed Online 24:61–65
Li J, Lu H, Tao F, Zhou H, Feng G, He L, Zhou L (2013) Meta-analysis of MMP9-1562C/T and the risk of coronary heart disease. Cardiology 124:53–59
Gong LL, Liu H, Liu LH (2014) Lack of association between matrix metalloproteinase-9 gene-1562C/T polymorphism and preeclampsia: a meta-analysis. Hypertens Pregnancy 33:389–394
Yang TF, Guo L, Wang Q (2014) Meta-analysis of associations between four polymorphisms in the matrix metalloproteinases gene and gastric cancer risk. Asian Pac J Cancer Prev 15:1263–1267
Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61
Wang L, Ma YT, Xie X, Yang YN, Fu ZY, Liu F, Li XM, Chen BD (2011) Association of MMP-9 gene polymorphisms with acute coronary syndrome in the Uygur population of China. World J Emerg Med 2:104–110
Emanuele E, Lista S, Ghidoni R, Binetti G, Cereda C, Benussi L, Maletta R, Bruni AC, Politi P (2011) Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer’s disease. Neurobiol Aging 32:1231–1235
Emanuele E, Bertona M, Geroldi D (2010) A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite. J Eur Acad Dermatol Venereol 24:930–935
Schveigert D, Valuckas KP, Kovalcis V, Ulys A, Chvatovic G, Didziapetriene J (2013) Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer. Tumori 99:523–529
Chiranjeevi P, Spurthi KM, Rani NS, Kumar GR, Aiyengar TM, Saraswati M, Srilatha G, Kumar GK, Sinha S, Kumari CS, Reddy BN, Vishnupriya S, Rani HS (2014) Gelatinase B (−1562C/T) polymorphism in tumor progression and invasion of breast cancer. Tumour Biol 35:1351–1356
El Samanoudy A, Monir R, Badawy A, Ibrahim L, Farag K, El Baz S, Alenizi D, Alenezy A (2014) Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses. Genet Mol Res 13:8025–8034
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Avcı, N., Ture, M., Deligonul, A. et al. Association and Prognostic Significance of the Functional −1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer. Pathol. Oncol. Res. 21, 1243–1247 (2015). https://doi.org/10.1007/s12253-015-9950-7
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DOI: https://doi.org/10.1007/s12253-015-9950-7