Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (-1562) C/T promoter polymorphisms

Susceptibility and prognostic implications in nasopharyngeal carcinomas

Hela Ben Nasr, Souhir Mestiri, Karim Chahed, Noureddine Bouaouina, Sallouha Gabbouj, Majida Jalbout, Lotfi Chouchane

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. Methods: The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. Results: No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR = 2.27; p = 0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR = 2.90; p = 0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p = 0.03). Conclusions: The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalClinica Chimica Acta
Volume384
Issue number1-2
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 1
Polymorphism
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Genetic Promoter Regions
Disease-Free Survival
Tumors
Genotype
Neoplasm Metastasis
Neoplasms
Genetic Markers
Extracellular Matrix
Nasopharyngeal carcinoma
Healthy Volunteers
Peptide Hydrolases
Multivariate Analysis
Genes
Lymph Nodes
Alleles
Survival

Keywords

  • MMPs
  • Nasopharyngeal Carcinoma
  • Polymorphism
  • Prognosis
  • Susceptibility

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (-1562) C/T promoter polymorphisms : Susceptibility and prognostic implications in nasopharyngeal carcinomas. / Nasr, Hela Ben; Mestiri, Souhir; Chahed, Karim; Bouaouina, Noureddine; Gabbouj, Sallouha; Jalbout, Majida; Chouchane, Lotfi.

In: Clinica Chimica Acta, Vol. 384, No. 1-2, 09.2007, p. 57-63.

Research output: Contribution to journalArticle

Nasr, Hela Ben ; Mestiri, Souhir ; Chahed, Karim ; Bouaouina, Noureddine ; Gabbouj, Sallouha ; Jalbout, Majida ; Chouchane, Lotfi. / Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (-1562) C/T promoter polymorphisms : Susceptibility and prognostic implications in nasopharyngeal carcinomas. In: Clinica Chimica Acta. 2007 ; Vol. 384, No. 1-2. pp. 57-63.
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abstract = "Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. Methods: The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. Results: No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR = 2.27; p = 0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR = 2.90; p = 0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p = 0.03). Conclusions: The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.",
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T1 - Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (-1562) C/T promoter polymorphisms

T2 - Susceptibility and prognostic implications in nasopharyngeal carcinomas

AU - Nasr, Hela Ben

AU - Mestiri, Souhir

AU - Chahed, Karim

AU - Bouaouina, Noureddine

AU - Gabbouj, Sallouha

AU - Jalbout, Majida

AU - Chouchane, Lotfi

PY - 2007/9

Y1 - 2007/9

N2 - Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. Methods: The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. Results: No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR = 2.27; p = 0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR = 2.90; p = 0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p = 0.03). Conclusions: The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.

AB - Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas. Methods: The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. Results: No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR = 2.27; p = 0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR = 2.90; p = 0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p = 0.03). Conclusions: The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.

KW - MMPs

KW - Nasopharyngeal Carcinoma

KW - Polymorphism

KW - Prognosis

KW - Susceptibility

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