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Background   Malignant pleural mesothelioma (MPM) is a rare disease with a relatively short overall survival (OS). Metalloproteinases (MMPs) have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of  MMP  genes could also serve as a prognostic biomarker in MPM.Methods   We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in  MMP2;  rs17576, rs17577, rs20544, and rs2250889 in  MMP9 ; and rs1042703, rs1042704, and rs743257 in  MMP14 . We determined the influence on survival using Cox regression.Results   Carriers of polymorphic  MMP9  rs2250889 allele had shorter time to progression (TTP) (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45–4.14,  p  = 0.001) and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37–4.18,  p  = 0.002). In contrast, carriers of at least one polymorphic  MMP9  rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38–0.86  p  = 0.007) and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37–0.85,  p  = 0.007).  MMP14  rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06–4.12,  p  = 0.032).Conclusions   Selected  MMP  SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.

Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma