Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma

Our plain-English summary of Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma, by D. Strbac, K. Goricar, V. Dolzan, et al (Radiology and Oncology, 2018).

The study

• Authors: D. Strbac, K. Goricar, V. Dolzan, V. Kovac
• Journal: Radiology and Oncology
• Published: 2018;52(2):160-166
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This Slovenian study compared the genes of people with malignant mesothelioma with those of healthy people. It included 236 patients with pleural or peritoneal mesothelioma (20 peritoneal) diagnosed and treated between 2007 and 2016, and 161 healthy blood donors aged 49 to 65. The authors tested ten variations in three genes, MMP2, MMP9 and MMP14. Patients were grouped as having no known asbestos exposure or known occupational or environmental exposure. Fiber types were not reported, and exposure data for the controls were lacking. Patients carrying at least one copy of the MMP2 rs243865 variant tended to have a lower mesothelioma risk (odds ratio 0.66, 95% CI 0.44 to 1.00; P = 0.050). When only asbestos-exposed patients were compared with the controls, the odds ratio was 0.55 (95% CI 0.35 to 0.86; P = 0.009). No other variant tested showed an association. The authors concluded that this variant may have a protective role in malignant pleural mesothelioma, more evident with asbestos exposure. They noted a small sample, a control group that was not age balanced, a low rate of patient asbestos exposure and missing control exposure data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective case-control genetic association study (patients compared with healthy blood donors)
• Who was studied: 236 patients with histologically confirmed pleural or peritoneal mesothelioma (20 peritoneal) diagnosed and treated 2007 to 2016, treated at the Institute of Oncology Ljubljana, Slovenia; 161 unrelated healthy Slovenian blood donors aged 49 to 65 as controls
• Exposure: Ten polymorphisms in the MMP2, MMP9 and MMP14 genes. Asbestos exposure was recorded only as known occupational or environmental exposure versus no known exposure: 169 patients exposed, 61 not exposed, 6 missing. No fiber types are given.
• Main results:
  • All patients versus controls: carriers of at least one polymorphic MMP2 rs243865 allele (CT+TT) tended to have a decreased mesothelioma risk, OR 0.66 (95% CI 0.44 to 1.00; P = 0.050). This was 81 of 236 patients (34.3%) versus 71 of 161 controls (44.1%).
  • Patients with known asbestos exposure versus controls: carriers of at least one polymorphic MMP2 rs243865 allele had significantly lower risk, OR 0.55 (95% CI 0.35 to 0.86; P = 0.009). This was 51 of 169 exposed patients (30.2%).
  • None of the other nine polymorphisms tested showed an association with mesothelioma risk.
  • In haplotype analysis, no significant associations were found. Haplotypes including the polymorphic MMP2 rs243865 allele had slightly lower risk, but this did not reach statistical significance.
• The authors' conclusion: The authors concluded that the MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma. They said the finding was more pronounced in asbestos-exposed patients, implying a strong gene-environment interaction.
• Limitations the authors state:
  • Small sample size, and a control group that was not appropriately age balanced (controls were significantly younger than patients)
  • Low rate of patient asbestos exposure, and no asbestos exposure data for the control group
  • Because the study was exploratory, no adjustments for multiple comparisons were made

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Carcinogenesis, Biomarker, Overall Survival, Odds Ratio, confidence interval.

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