Analysis of Matrix Metalloproteinase-1 Gene Polymorphisms and Expression in Benign and Malignant Breast Tumors

Abstract

A guanine insertion polymorphism in matrix metalloproteinase-1 promoter (MMP-1 2G) is linked to early onset and aggressiveness in cancer. We determined the role of MMP-1 2G on the level of MMP-1 expression and breast cancer severity in benign breast disease, atypical hyperplasia, invasive and non invasive (in situ) breast cancer. We observed no significant difference in genotype distribution among the different breast disease groups. However, the level of MMP-1 expression was significantly higher in atypical ductal hyperplasia compared to benign breast disease; and in invasive breast cancer compared to in situ breast cancer. MMP-1 2G insertion polymorphism in the invasive group also correlated significantly with the expression of MMP-1 and breast cancer prognostic markers HER2 and P53.

The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan

“…In normal conditions, MMP1 is under the suppression of TIMP1 (43,44) and elevated MMP1 has been reported to play an important role in invasive and migration capacity of tumor cells (45). Mounting evidence indicates that elevated MMP1 expression was observed in the borders of solid tumors, such as breast and oral cancer (46)(47)(48). Mechanically, MMP1 is thought to promote invasion and metastasis through the degradation of the ECM as the main component of connective tissue, like to relieve the reins for the horses (49)(50)(51).…”

MMP1 rs1799750 Single Nucleotide Polymorphism and Lung Cancer Risk: A Meta-analysis

“…One allele has one guanine (1G), and the other one has two guanines (2G). The additional guanine (2G) creates an Ets-binding site, increases the transcription activity, and therefore, 2 G is associated with high level of MMP1 expression (Zhou et al, 2011). Increased MMP-1 activity enables greater ECM degradation, cell growth factor activation, and tumor cell immune escape, which facilitate the initiation and invasiveness of cancer (Yamamura et al, 2002).…”

“…Increased MMP-1 activity enables greater extracellular matrix (ECM) degradation, cell growth factor activation, and tumor cell immune escape, which facilitate the initiation and invasiveness of cancer (Yamamura et al, 2002). MMP1 gene is polymorphic, and a number of single nucleotide polymorphisms (SNPs) have been identified, and are potentially functional and been studied for their associations with cancer susceptibility and cancer metastasis (Zhou et al, 2011, Liu et al, 2012. A single-guanine 2G to 1G polymorphism located at the MMP-1 promoter region (SNP rs1799750) has been identified that affects the transcription level of the gene (Zhou et al, 2011).…”

“…MMP1 gene is polymorphic, and a number of single nucleotide polymorphisms (SNPs) have been identified, and are potentially functional and been studied for their associations with cancer susceptibility and cancer metastasis (Zhou et al, 2011, Liu et al, 2012. A single-guanine 2G to 1G polymorphism located at the MMP-1 promoter region (SNP rs1799750) has been identified that affects the transcription level of the gene (Zhou et al, 2011). It has been demonstrated that the promoter comprising the 2G allele has significantly greater transcriptional activity compared with the 1G promoter, because the 2G allele creates a transcription factor binding site and increases transcription capacity (Su et al, 2006;Chen et al, 2012).…”

Functional Gene Polymorphism of Matrix Metalloproteinase-1 Is Associated with Benign Hyperplasia of Myo- and Endometrium in the Russian Population

“…The 2G (insertion) allele exhibits an additional binding site for Ets, an estrogen-sensitive transcription factor, thus providing higher synthesis of pro-MMP-1 mRNA (Ye et al, 2001). A homozygous 2G/2G state is found to be associated with a higher risk of invasion and/or metastases in several types of malignant tumors (Fingleton, 2006;Zhou et al, 2011). Similarly, an MMP-3 gene polymorphism displays functional variants at the -1171 position (5A/6A genotype).…”