Association of Matrix Metalloproteinase-2 Genotypes With Prostate Cancer Risk

Abstract

Background/Aim: Prostate cancer is one of the most commonly diagnosed malignancies among males, especially in Western populations. Matrix metalloproteinase-2 (MMP-2) plays a critical role in extracellular regulation and metastasis. However, its genotypes have seldom been examined among patients with prostate cancer (PCa). Therefore, the purpose of the study was to evaluate the association of genotypes at MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) with PCa risk in a Taiwanese cohort. Materials and Methods: The profiles of MMP-2 rs243865 and rs2285053 genotypes were examined among 218 PCa patients and 436 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodologies. Results: The percentages of wildtype CC, and variant CT and TT genotypes on MMP-2 rs243865 were 88.5, 10.6, and 0.9% in the PCa case group and 85.6, 13.5, and 0.9% in the control group, respectively (p for trend=0.5544). The allelic frequency distribution showed that the variant T allele at MMP-2 rs24386 5 was not associated with PCa risk (p=0.3250). As for MMP-2 rs2285053, the results were also non-significant. In addition, there was no association between the genotypes of MMP-2 rs243865 or rs2285053 with age or smoking status on PCa risk. Conclusion: rs11568818 and rs11568819 at MMP-2 promoter region played minor roles in determining individual PCa risk.Prostate cancer (PCa) is the second most prevalent malignancy, and the fifth leading death-causing cancer among males worldwide, with about 1,414,000 newly diagnosed cases and 375,304 deaths in 2020 (1). According to global cancer statistics, PCa is the most frequently diagnosed cancer in 112 countries, and the leading death-causing malignancy in 48 countries including USA (2). According to world cancer statistics, PCa cases are predicted to continue to increase due to the trend of global aging (3). From the epidemiological viewpoint, black race, family cancer history, and aging, are three most well-known risk factors for PCa (4). In addition, fitness (5), diabetes mellitus (6), obesity (7), risky diet (8), and over-supplementation of vitamin E (9) may also contribute to the etiology of PCa. However, lack of targets in PCa therapy urge the identification of genetic markers.The extracellular matrix (ECM) is a meshwork of crosslinked macromolecules that form a dynamic scaffold outside of the cells. It provides homeostasis of the micro-environment, and its imbalances may associate with cancer progression and metastasis (10,11). Noticeably, matrix metalloproteinases (MMPs, also named matrix metallopeptidases or matrixins) play 343 *These Authors contributed equally to this study.

Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer

“… 11 Tumor metastasis and matrix metalloproteinase-2 (MMP-2) are closely related, as MMP-2 can degrade the basement membrane and extracellular matrix, resulting in endothelial cell migration. 12 MMP-7 plays a role in human cancer. 13 MMP-9 promotes angiogenesis and tumor growth and regulates cell migration.…”

Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer

“…The main studied polymorphisms of MMP-2 are rs243865 and rs2285053, which are located in the MMP-2 promoter at positions -1306 and -735, respectively, while the MMP-9 polymorphism rs3918242 is located in the MMP-9 promoter at position -1562, all of which induce the transition of the allele C to T [ 25 ]. MMP-2 and MMP-9 promoter polymorphisms can affect mRNA and protein expression levels by modifying transcriptional activity, eventually leading to the development of several types of cancer, including breast, lung, esophageal, and colorectal cancer [ 29 , 30 , 31 , 32 ]. According to growing research, MMP-2 appears to also have a key role in the metastasis of a number of malignancies, including glioma and colorectal cancer [ 33 , 34 ].…”