Matrix metalloproteinase-1(-1607) 1G/2G and -9(1562) C/T promoter polymorphisms: Susceptibility and prognostic implications in nasopharyngeal carcinomas

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. (c) 2007 Elsevier B.V. All rights reserved.