Alakus, Hakan, Afriani, Noor, Warnecke-Eberz, Ute, Bollschweiler, Elfriede, Fetzner, Ulrich, Drebber, Uta, Metzger, Ralf, Hoelscher, Arnulf H. and Moenig, Stefan P. (2010). Clinical Impact of MMP and TIMP Gene Polymorphisms in Gastric Cancer. World J.Surg., 34 (12). S. 2853 - 2860. NEW YORK: SPRINGER. ISSN 1432-2323

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Abstract

Background Recent studies suggest that single-nucleotide polymorphisms (SNPs) within matrix metalloproteinase (MMP) genes and genes of tissue inhibitors of metalloproteinases (TIMPs) have an impact on the expression of these genes and on the prognosis for gastric cancer. Methods Genomic DNA was extracted from paraffin-embedded tissues of 135 patients who were treated surgically for primary gastric carcinoma. Genotyping was performed for MMP-2(-1306C>T), TIMP-2(303C>T), and MMP-7(-181A>G). MMP-2 and TIMP-2 antigen expression in resected tumor tissues was detected immunohistochemically. Genotyping was correlated with antigen expression, histopathologic parameters, and prognosis. Results The SNPs did not correlate with tumor differentiation, pT, R category, or the classifications according to the International Union Against Cancer (UICC), the World Health Organization (WHO), and Lauren and Ming. A significant correlation was observed for TIMP-2(303C>T) with higher pN stages (p = 0.01) and more distant metastasis (p = 0.02) for patients with the CC genotypes. In univariate analysis, patients with the TIMP-2(303C>T) CC genotype had an inferior survival, that was not significant (p = 0.2). However, among the gastric cancer patients in the present study, MMP-2(-1306C>T) significantly correlated with gender, with men having more CC genotypes than women (p = 0.025). There were no significant correlations between genotype and protein levels of MMP-2 (p = 0.766) and TIMP-2 (p = 0.684). Conclusions The TIMP-2(303C>T) CC genotype is associated with higher pN and pM categories and, in contrast to previous studies, with worse survival in gastric cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Alakus, HakanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Afriani, NoorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warnecke-Eberz, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bollschweiler, ElfriedeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fetzner, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzger, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelscher, Arnulf H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moenig, Stefan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-492139
DOI: 10.1007/s00268-010-0761-4
Journal or Publication Title: World J.Surg.
Volume: 34
Number: 12
Page Range: S. 2853 - 2860
Date: 2010
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-2323
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MATRIX METALLOPROTEINASES; FUNCTIONAL POLYMORPHISM; POOR-PROGNOSIS; METASTASIS; EXPRESSION; SURVIVALMultiple languages
SurgeryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49213

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