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Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Danijela Strbac

Danijela Strbac

Institute of Oncology LjubljanaLjubljana, Slovenia
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Strbac, Danijela
, 
Katja Goricar

Katja Goricar

Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Goricar, Katja
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Vita Dolzan

Vita Dolzan

Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Dolzan, Vita
 e 
Viljem Kovac

Viljem Kovac

Institute of Oncology LjubljanaLjubljana, Slovenia
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Kovac, Viljem
  
07 feb 2018
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Categoria dell'articolo: Research Article
Pubblicato online: 07 feb 2018
Pagine: 160 - 166
Ricevuto: 10 dic 2017
Accettato: 17 dic 2017
DOI: https://doi.org/10.2478/raon-2018-0005
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© 2018 Danijela Strbac, Katja Goricar, Vita Dolzan, Viljem Kovac, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Background

Malignant 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 methods

The 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).

Results

Carriers 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.

Conclusions

The 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.
Lingua:
Inglese
Frequenza di pubblicazione:
4 volte all'anno
Argomenti della rivista:
Medicina, Medicina clinica, Medicina interna, Ematologia, Oncologia, Radiologia
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