A Study on Polymorphisms in the Matrix Metalloproteinase MMP and Inflammatory Genes and their Possible Relationship to Colorectal Cancer Risk in Kashmiri Population

Abstract

Colorectal cancer (CRC) also known as colon cancer or large bowel cancer includes the neoplasia of the colon, rectum and appendix and is one of the most common cancers and leading cause of cancer related mortality and morbidity worldwide. Matrix metalloproteinases (MMPs), a family of zinc dependent endopeptidases and their physiological inhibitors including tissue inhibitors of metalloproteinases (TIMPs) are key players in the coordinated proteolytic breakdown and remodeling of extracellular matrix (ECM) and basement membrane which besides making them important for several physiological processes also makes them vital for tumor invasiveness and metastasis. Besides, they also play a critical role in several other stages of tumor development and progression. MMPs have also been associated with tumor aggressiveness and the increased expression and activity of MMPs have been described in almost every type of human cancer including colorectal cancer. Several studies have demonstrated that the functional single-nucleotide polymorphisms (SNPs) in the promoter regions of various MMPs including MMP2, MMP7, MMP9 and TIMPs including TIMP2 and TIMP3 have pivotal allele-specific effects on the regulation of MMP and TIMP gene transcription that in turn leads to altered gene expression, secretion, activity and function of these MMPs and TIMPs and confer differences in susceptibility between different individuals to several diseases including various cancers such as colorectal cancer. Colorectal cancer is one of the few cancers in which inflammation is mostly evident as a basic pathological incident at the earliest stages of tumor progression and is capable of transforming the pre-neoplastic lesions characteristic of colorectal tumorigenesis into aggressively invasive tumors. Inflammation is of frequent occurrence in the colorectal tissues and the development of CRC has a strong association with innate immune processes and intestinal inflammation. Several inflammation related pathological conditions and disorders, in particul...