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Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma: A Comprehensive Review

Vasiliki Panou1,2,3, Oluf Dimitri Røe3,4

  • 1Department of Respiratory Medicine, Odense University Hospital, 5000 Odense, Denmark.

International Journal of Molecular Sciences
|June 21, 2020
PubMed

Insights

Genetic susceptibility plays a role in malignant mesothelioma (MM) risk beyond asbestos exposure. This review highlights germline mutations in DNA repair genes and tumor suppressors, offering insights for early detection and targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Environmental Health

Background:

  • Malignant mesothelioma (MM) is primarily linked to asbestos exposure, but genetic factors are increasingly recognized as contributing to susceptibility.
  • While BRCA1-associated protein-1 (BAP1) is a known gene linked to MM, numerous other candidate genes are emerging.
  • Understanding inherited predispositions is crucial for comprehensive MM risk assessment.

Purpose of the Study:

  • To review and summarize key studies identifying germline mutations associated with malignant mesothelioma.
  • To consolidate current knowledge on genetic factors influencing MM development.
  • To explore the role of specific gene pathways and single nucleotide polymorphisms (SNPs) in MM pathogenesis.

Main Methods:

  • A systematic literature search was conducted across Scopus, PubMed, and Web of Science.
  • 860 publications were initially identified, with 81 meeting the inclusion criteria for the review.
  • Analysis focused on germline mutations, candidate genes, and their functional pathways.

Main Results:

  • Over 50% of identified predisposing genes are involved in DNA repair, particularly the homologous recombination pathway.
  • Genetic alterations in tumor suppressor genes regulating chromatin, transcription, and hypoxia were also noted.
  • Specific single nucleotide polymorphisms (SNPs) in DNA repair and carcinogen detoxification genes may interact with asbestos exposure to promote MM.

Conclusions:

  • Germline mutations in various genes, especially those involved in DNA repair, contribute to malignant mesothelioma susceptibility.
  • The identification of these inherited mutations and associated pathways is vital for early detection and prevention strategies in high-risk populations.
  • Further research into these genetic factors could lead to the development of novel, targeted therapeutic approaches for MM.
Keywords:
genetic cancer susceptibilityinherited genetic mutationsmalignant mesotheliomasingle nucleotide polymorphisms

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