Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma
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), overall survival (OS), and 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: MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. Predicted function of these polymorphisms was assessed using Single Nucleotide Polymorphism (SNP) Function Prediction.In statistical analyses continuous and categorical variables were described using median and range (25%‒75%) and frequencies, respectively. 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). Statistical significance was reached only for MMP2 rs243865. None of the other tested polymorphisms have reached statistical significance.
Conclusions. The rs243865 has a possible protective role in malignant mesothelioma. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction