Genetic Polymorphisms in Matrix Metalloproteinase (MMP) Genes and Cancer

Abstract

Matrix metalloproteinases (MMPs) constitute an important family of endopeptidases in humans and other primates. MMPs together process or cleave almost all the components of the basement membrane (BM) and the extracellular matrix (ECM) and various non-matrix bioactive substrates. Most of the MMP-processed ECM components and soluble protein mediators play crucial roles in numerous cellular signaling pathways and, therefore, regulate a multitude of physiological processes that depend on these cellular signaling pathways. Consequently, dysfunction or dysregulation of MMPs promote various pathophysiological conditions that often manifest as varied diseases or disorders including cancers of almost all the types. MMPs, predominantly through the proteolysis of diverse substrates, play a critical role in almost all the important pro-tumorigenic processes including tumor growth and progression, apoptosis, angiogenesis, activation and promotion of tissue invasion and metastasis and escape of tumor cells from different immunesurveillance mechanisms. Various single nucleotide polymorphisms (SNPs) in MMP genes have the potential to modulate gene transcription, 140expression and subsequently serum levels and enzyme activity of MMPs in an allele-specific manner. The allele-specific differences that result in increased or decreased physiological levels and functions of MMPs may possibly modulate the risk of various cancers. In this chapter, we briefly discuss the MMP family, its structure, classification and regulation. We also discuss the role of some prominent members of MMP family in the pathogenesis of various cancers and review the outcome of various association studies that evaluated the role of SNPs in the genes encoding these MMPs in modulating the risk for the development of various cancers.