Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer.
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 Laurén 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.
Alakus
Hakan
H
Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology, University of Cologne, Kerpenerstrasse 62, 50937, Cologne, Germany. hakan.alakus@uk-koeln.de
Afriani
Noor
N
Warnecke-Eberz
Ute
U
Bollschweiler
Elfriede
E
Fetzner
Ulrich
U
Drebber
Uta
U
Metzger
Ralf
R
Hölscher
Arnulf H
AH
Mönig
Stefan P
SP
D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2