BERKELEY, CA (UroToday.com) - The human matrix metalloproteinases (MMPs) are zinc enzymes comprising a large family of 24 extracellular proteinases. MMPs are considered to play prominent roles in many biological processes, including physiological processes and pathogenesis. MMPs are responsible for hydrolyzing of the extracellular matrix (ECM) components: in normal embryogenesis, morphogenesis, normal tissue remodeling such as wound healing and scar formation, and in many morbid processes. These enzymes are synthesized, depending on conditions, by different cell types and also by tumor cells. Studies have demonstrated that altered structural components of cellular microenvironment and blood vessel basement membranes are required for primary tumor growth, angiogenesis, and formation of tumor metastases. Reports from earlier research have suggested that the MMPs can release signaling molecules such as chemokines, cytokines, growth factors, their receptors and other MMPs from the ECM. Furthermore, MMPs may proteolytically convert those molecules. It is generally recognized that the processes play a major role in the genesis of cancer.
The family of tissue inhibitors of metalloproteinases (TIMP) is comprised of 4 members. They play an important role in the homeostasis of ECM and in tumorigenesis by inhibiting MMP activity. However, it has been also shown that TIMPs are multifunctional, since they can stimulate cell proliferation, apoptosis, angiogenesis, and activation of the MMP2 zymogen.
Single nucleotide polymorphism (SNP) is the most common type of changes in DNA sequence, which occurs in more than 1% of humans. Notably, some functionally important genotypes could lead to differences in transcriptional activity, mRNA stability, and amino acid substitution. This can determine differences in gene expression levels and protein levels. Therefore, it is reasonable to conclude that the single or combined SNPs may contribute to cancer susceptibility.
This article presents the results from case-control study of the relationship between the genetic polymorphisms of the MMPs and TIMPs, and susceptibility to bladder cancer (BC). To test the hypothesis that functional polymorphisms of the MMPs: MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109), and TIMPs: TIMP1 (rs2070584) and TIMP3 (rs9619311) genes could be involved in the risk of BC, we genotyped 199 unrelated controls and 241 BC patients. We examined the joint effects of the genotypes and smoking status on BC risk, association of genotype with different histological grade, and combined effect of genotypes and BC risk.
Our findings suggest that only genetic variation in MMP1 (rs1799750) influences the susceptibility to BC in the ethnically homogeneous Polish population. None of the remaining 5 polymorphisms of MMPs and TIMPs were significantly associated with BC risk.
Edyta Wieczorek and Edyta Reszka as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland