Colorectal Carcinoma Susceptibility and Metastases Are Associated with Matrix Metalloproteinase-7 Promoter Polymorphisms

Tumor invasion and metastasis are important aspects of tumor progression, and the formation of tumor metastasis is a principal contributing factor to cancer morbidity and mortality (1). Basal membrane and extracellular matrix represent two physical barriers to malignant invasion: their degradation by matrix metalloproteinases (MMPs) plays a key role in tumor progression and metastatic spread (2)(3).MMP expression in tumors is regulated in a paracrine manner by growth factors and cytokines secreted by tumor-infiltrating inflammatory cells as well as by tumor or stromal cells. Recent studies have suggested continuous cross-talk between tumor cells, stromal cells, and inflammatory cells during the invasion process (1)(2)(4)(5). Expression of most MMPs is usually low in tissues and is induced when remodeling of extracellular matrix is required. MMP gene expression is primarily regulated at the transcriptional level, but there is also evidence of modulation of mRNA stability in response to growth factor and cytokines (2)(6).Several lines of evidence indicate a significant association between variations in MMP genes and susceptibility to cancer. The promoter region of inducible MMP genes (i.e., MMP1 and MMP3 ) shows remarkable conservation of regulatory elements, and their expression is induced by growth factors, cytokines, and other environmental factors, such as contact with extracellular matrix (7)(8)(9).Recently, a naturally occurring sequence variation in the human MMP1 gene promoter was reported (10). Many studies have demonstrated the correlation between the 2G allele and several malignant tumors with different histogenetic origins (11)(12)(13)(14)(15). Recently, our group demonstrated a correlation between the MMP3 polymorphism and breast cancer (16).Matrilysin (MMP7) is a protease with broad substrate specificity, being able to degrade elastin, proteoglycans, fibronectin, and type IV collagen. MMP7 is …