Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrixproteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306,which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with theT allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associatedwith susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expressionlevel sin CRC patients and 4 different cancer cell lines. Materials and
Methods: TaqMan allele discriminationassays and DNA sequencing techniques were used to investigate the C-1306T SNP in the MMP-2 gene of Saudicolorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 coloncancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumormargins. Results and
Conclusions: The MMP-2 C-1306T SNP in the promoter region was associated with CRC inour Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients.The MMP-2 C-1306T SNP is significantly associated with CRC in the Saudi population and this finding suggestedthat MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of thisgene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.