DNA repair systems in malignant mesothelioma

Our plain-English summary of DNA repair systems in malignant mesothelioma, by D. Toumpanakis, S.E. Theocharis (Cancer Letters, 2011).

The study

• Authors: D. Toumpanakis, S.E. Theocharis
• Journal: Cancer Letters
• Published: 2011;312(2):143-9
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumor of serosal surfaces with increasing incidence and poor prognosis. Asbestos exposure is the main cause of MM and asbestos-induced DNA damage is critical for MM pathogenesis. The present review summarizes the implications of DNA repair systems in MM development, focusing on gene expression alterations and single nucleotide polymorphisms of genes encoding for DNA repair enzymes. The involvement of DNA repair systems in MM improves understanding of MM pathogenesis and provides novel therapeutical targets.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This article was a mini-review by two authors from the National and Kapodistrian University of Athens. It summarized published research on the systems cells use to repair damaged DNA, and how these systems may relate to malignant mesothelioma. The authors described asbestos exposure as the main cause of this cancer. The review reported no new data of its own. It described laboratory, animal and human studies carried out by others. In one cited study of asbestos-exposed subjects, a gene variant called XRCC1-399Q was linked to increased mesothelioma risk (odds ratio 2.15, confidence intervals 1.08–4.28). Another study found no correlation when this was assessed independently of asbestos exposure. A meta-analysis of two studies linked an APE gene variant to mesothelioma (odds ratio 1.72, 95% confidence intervals 1.02–2.91). Many other variants showed no significant correlation. One cited study found MGMT promoter methylation in 13 of 95 pleural mesothelioma biopsies. The authors concluded that the involvement of DNA repair systems improves understanding of mesothelioma and provides possible new treatment targets.

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: Mini-review (narrative review of published studies; no search method described, no new data)
• Who was studied: No study population of its own. The review summarized published laboratory (cell line), animal (rat, mouse) and human studies of DNA repair genes in malignant mesothelioma.
• Exposure: Asbestos in general, including crocidolite asbestos in cited laboratory studies and mineral fibers including asbestos in one cited worker study. The review focused on DNA damage caused by asbestos and on variation in DNA repair genes.
• Main results:
  • A cited study (ref. 25) reported increased mesothelioma risk among asbestos-exposed subjects for the XRCC1-399Q variant: OR 2.15, CIs 1.08–4.28.
  • Another cited study (ref. 31) found no correlation between XRCC1-399Q and mesothelioma when this was assessed independently of asbestos exposure.
  • Two studies of the APE D148E variant individually showed no significant results. A meta-analysis of the two (ref. 30) found a significant correlation with mesothelioma: OR 1.72, 95% CIs 1.02–2.91.
  • A cited study (ref. 30) reported a significant correlation of the ERCC1 N118N variant with mesothelioma in heterozygotes: OR 1.59, CIs 1.01–2.50.
  • A cited study (ref. 31) found no significant correlations between mesothelioma and variants of several other repair genes, including mismatch repair genes MLH1, MSH2, MSH3 and MSH6, and homologous recombination genes including BRCA1 and BRCA2.
  • A cited study by Kristensen et al. detected MGMT promoter methylation in biopsies from 13 of 95 patients with pleural mesothelioma. Gene silencing was rare.
  • A cited gene expression analysis (ref. 42) reported upregulation in mesothelioma of several repair genes, including RAD50, RAD54L, RAD21 and BRCA2.
• The authors' conclusion: The authors concluded that DNA repair systems are involved in mesothelioma development. In their view, defective repair (from lowered gene expression or gene variants) may act together with asbestos exposure. Increased repair activity may raise tumor resistance to chemotherapy and radiotherapy. Blocking repair enzymes could offer new treatment targets.
• Limitations the authors state:
  • The authors noted a lack of evidence in the literature on the role of the mismatch repair system in mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Serosal Surface, Prognosis, Asbestos Exposure.

Related studies

• DNA repair polymorphisms and treatment outcomes of patients with malignant mesothelioma treated with gemcitabine-platinum combination chemotherapy — N. Erčulj, V. Kovač, et al. (2012)
• Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies — M. Dusinska, M. Staruchova, et al. (2012)
• Is DNA repair a potential target for effective therapies against malignant mesothelioma? — I. Fuso Nerini, E. Roca, et al. (2020)
• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma — M. Betti, E. Casalone, et al. (2017)
• A Novel BRCA1-Associated Protein-1 Isoform Affects Response of Mesothelioma Cells to Drugs Impairing BRCA1-Mediated DNA Repair — R. Parrotta, A. Okonska, et al. (2017)

Browse more research in Cancer Letters, or return to medical research.