Genetic polymorphism of matrix metalloproteinases in breast cancer

Abstract

The family of human matrix metalloproteinases (MMPs) consists of 24 zinc-and calcium-dependent proteolytic enzymes. MMPs are divided into six subgroups, in terms of differences in the substrate specificity with structural domain architecture. These enzymes are involved in many physiological processes, such as skeletal development, wound healing, scar formation, as well as carcinogenesis. MMPs, fulfilling its function of degradation of extracellular matrix components, are involved in one of the stages of angiogenesis enabling the development, growth and spread of the primary tumor. Therefore, the search for the common polymorphic variants of MMPs, new genetic markers as prognostic factors in breast cancer progress seems to be understandable.The minireview presents the results of 19 case-control or prospective studies concerning the association of SNPs of genes encoding nine MMPs: MMP-1, -2, -3, -7, -8, -9, -12, -13, -21 with the breast cancer risk, progression and survival. Key words: matrix metalloproteinases, genetic polymorphism, breast cancerBreast cancer, one of the leading civilization diseases, has for a number of years already focused attention of clinicians and researchers. It is the most commonly diagnosed cancer in women and is the major cause of death among female cancer patients. GLOBCAN estimates that, among the 12.7 million cancer cases worldwide in 2008, 2.9 million were women with breast cancer, and a million died of this cancer [1]. It is estimated that approximately 10% of the incidence of breast cancer is genetically-related and in most of the cases results from mutations in the genes BRCA1, BRCA2, p53, ATM. Attention should also be paid to a number of environmental factors related to diet and occupational exposure, including tobacco smoking, alcohol intake, obesity, shift work at night. Factors considered in the etiology of breast cancer include also endogenous hormonal factors, such as age of occurrence of menarche, menopause, number of births, and exogenous hormonal factors such as use of hormonal contraceptives or hormonal replacement [2,3]. Currently, a description of cancer cases includes clinical stage and Tumor Nodus Metastases (TNM) clinical classification, hormone receptor status and BRCA1, BRCA2 mutations. All these indicators are still not sufficient to predict the course of the cancer and, therefore, it is important to search for new markers that will enable the patient's prognosis and new predictive markers of cancer risk. As the majority of breast cancer deaths are caused by the invasion of cancer to other, sometimes distant organs, it is believed that it is appropriate to study the role of the enzyme gene polymorphisms that affect the process of angiogenesis largely responsible for the development, growth and metastatic capacity of the primary tumor. Key enzymes involved in these processes include the matrix metalloproteinases (MMPs) participating in an important stage of angiogenesis, namely the degradation of extracellular matrix (ECM) components.Matrix metalloproteinases. MM...

Analysis of the Association of Matrix Metalloproteinase-1 Gene Promoter (rs1799750) Polymorphism and Risk of Ovarian Cancer

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Human adipose-derived stem cell adipogenesis induces paracrine regulation of the invasive ability of MCF-7 human breast cancer cells in vitro

“…Breast cancer cells have been demonstrated to be closely associated with the expression of uPA, MMP-2, MMP-9 and VEGF (17,18). uPA enables extracellular matrix degradation by catalyzing the metalloproteinase precursors to activate MMP-9 (19,20) and enhancing endotheliocyte proliferation for blood vessel formation.…”

MMP1, 2, 3, 7, and 9 Gene Polymorphisms and Urinary Cancer Risk: A Meta-Analysis

“…These polymorphisms may affect the production or gene expression of these MMPs in an allele-specific manner (Piccoli et al, 2007;Tsuchiya et al, 2009;Wieczorek et al, 2013;Yaykas xli et al, 2014). Furthermore, there is an increasing evidence indicating that these functional polymorphisms may contribute to interindividual differences in a wide spectrum of cancer susceptibility (Decock et al, 2008;Pereira et al, 2012;Wieczorek et al, 2012).…”