Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

Štrbac, Danijela; Goričar, Katja; Dolžan, Vita; Kovač, Viljem

doi:10.1155/2017/8069529

Cited by 13 publications

(16 citation statements)

References 34 publications

(38 reference statements)

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“… 6 In a previous paper we studied the possible role of single nucleotide polymorphisms (SNPs) as potential markers of treatment response. 7 We identified MMP9 rs2250889, MMP9 rs20544 , MMP14 rs1042703 as statistically significantly associated with overall survival (OS) in MM. Carriers of the polymorphic MMP9 rs2250889 and MMP14 rs1042703 alleles had shorter OS, compared to non-carriers, while carriers of polymorphic MMP9 rs20544 allele had longer OS.…”

Section: Introductionmentioning

confidence: 96%

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Štrbac

Goričar

Dolžan

et al. 2018

Radiology and Oncology

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BackgroundMalignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure.Patients and methodsThe study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%–75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).ResultsCarriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44–1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35–0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.ConclusionsThe MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

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Section: Introductionmentioning

confidence: 96%

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Štrbac

Goričar

Dolžan

et al. 2018

Radiology and Oncology

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“…Furthermore, a study including 199 Slovenian malignant mesothelioma patients suggested that MMP polymorphisms may have a role as prognostic biomarkers in malignant mesothelioma, as carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression and shorter overall survival compared to noncarriers. In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer time to progression and longer OS (overall survival than noncarriers [112].…”

Section: Genes Involved In Matrix Remodellingmentioning

confidence: 89%

Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

Dolžan¹,

Franko²

2020

Diseases of Pleura

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Several pleural diseases have been associated with asbestos exposure. Asbestos exposure may lead to the development of benign pleural diseases, such as pleural plaques, diffuse pleural thickening, and pleural effusion, as well as to the development of malignant mesothelioma, a highly aggressive tumour of the pleura. Asbestos exposure related to pleural diseases may be occupational or environmental. Although the causal relationship between asbestos-related pleural diseases and asbestos exposure has been well confirmed, the role of genetic factors in the development of these diseases needs to be further investigated and elucidated. The results of the studies performed so far indicate that in addition to asbestos exposure, genetic factors as well as the interactions between genetic factors and asbestos exposure may have an important impact on the risk of asbestos-related pleural diseases, especially malignant mesothelioma. This chapter aims to present how the risk of developing asbestos-related pleural diseases may be influenced by asbestos exposure, genetic factors, interactions between different genetic factors, as well as interactions between different genetic factors and asbestos exposure.

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“…Many studies have identified molecular pathways and mutations important in MPM, including BAP1; yet, there remains a paucity of biomarkers that are currently in the clinical setting . Susceptibility and prognostic markers may allow personalized screening, detection, and treatment approaches, which have been a challenge for MPM that is typically diagnosed in its later stage.…”

Section: Discussionmentioning

confidence: 99%

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis

Lee

Kuehne

Hueniken

et al. 2019

Molecular Carcinogenesis

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Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM‐741/BRM‐1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos‐exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM‐741/BRM‐1321 and risk in patients with MPM, a differential effect by smoking status was observed (P‐interaction < .001), where homozygous variants were protective (aOR of 0.18‐0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7‐4.4). While there was no association between BRM polymorphisms and OS in ever‐smokers, the aHR of carrying homozygous‐variants of BRM‐741, BRM‐1321 or both were 4.0 to 8.6 in never‐smokers when compared to wild‐type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA‐affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never‐smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever‐smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.

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Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

Cited by 13 publications

References 34 publications

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis

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