The Role of Matrix Metalloproteinase-3 Functional 5A/6A Promoter Polymorphism in Tumor Cell Progression and Metastasis of Breast Cancer

In the human genome, chromosome 11 contains a cluster of matrix metalloproteinase (MMP) genes. Single nucleotide polymorphisms in the promoter region of MMP genes are important for MMP expression. A common adenine deletion polymorphism (5A) at position -1171 of the MMP-3 gene promoter (5´-AAAAAACCAT-3´ change to 5´-AAAAACCAT-3´) facilitates transcriptional factor binding and MMP-3 promoter activity. A case-control study was performed including 120 breast cancer patients (60 patients with metastatic activity and 60 patients without metastatic activity); and 60 healthy controls. Whole blood samples were obtained from patients and healthy controls. Genomic DNA was extracted from samples and the MMP-3 5A/6A genotypes were determined using PCR-RFLP. MMP-3 genotype distributions between patients and controls were similar (OR= 0.89, 95%CI, 0.43-1.84, P= 0.047). It was observed that the 5A allele was more frequent among patients with metastatic activity than controls (OR= 2.9, 95%CI, 0.94-8.9, P= 0.074). Therefore, the 5A polymorphism in the MMP-3 promoter showed correlation with the metastasis group than patients without metastasis; both at the time of diagnosis. However our results do not show evidence for correlation between 5A/6A polymorphism and breast cancer susceptibility.