TY - JOUR
T1 - Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma
T2 - A Comprehensive Review
AU - Panou, Vasiliki
AU - Røe, Oluf Dimitri
PY - 2020/6/17
Y1 - 2020/6/17
N2 - Malignant mesothelioma (MM) is mainly caused by air-born asbestos but genetic susceptibility is also suspected to be a risk factor. Recent studies suggest an increasing number of candidate genes that may predispose to MM besides the well-characterized BRCA1-associated protein-1 gene. The aim of this review is to summarize the most important studies on germline mutations for MM. A total of 860 publications were retrieved from Scopus, PubMed and Web of Science, of which 81 met the inclusion criteria and were consider for this review. More than 50% of the genes that are reported to predispose to MM are involved in DNA repair mechanisms, and the majority of them have a role in the homologous recombination pathway. Genetic alterations in tumor suppressor genes involved in chromatin, transcription and hypoxia regulation have also been described. Furthermore, we identified several single nucleotide polymorphisms (SNPs) that may promote MM tumorigenesis as a result of an asbestos-gene interaction, including SNPs in DNA repair, carcinogen detoxification and other genes previously associated with other malignancies. The identification of inherited mutations for MM and an understanding of the underlying pathways may allow early detection and prevention of malignancies in high-risk individuals and pave the way for targeted therapies.
AB - Malignant mesothelioma (MM) is mainly caused by air-born asbestos but genetic susceptibility is also suspected to be a risk factor. Recent studies suggest an increasing number of candidate genes that may predispose to MM besides the well-characterized BRCA1-associated protein-1 gene. The aim of this review is to summarize the most important studies on germline mutations for MM. A total of 860 publications were retrieved from Scopus, PubMed and Web of Science, of which 81 met the inclusion criteria and were consider for this review. More than 50% of the genes that are reported to predispose to MM are involved in DNA repair mechanisms, and the majority of them have a role in the homologous recombination pathway. Genetic alterations in tumor suppressor genes involved in chromatin, transcription and hypoxia regulation have also been described. Furthermore, we identified several single nucleotide polymorphisms (SNPs) that may promote MM tumorigenesis as a result of an asbestos-gene interaction, including SNPs in DNA repair, carcinogen detoxification and other genes previously associated with other malignancies. The identification of inherited mutations for MM and an understanding of the underlying pathways may allow early detection and prevention of malignancies in high-risk individuals and pave the way for targeted therapies.
KW - genetic cancer susceptibility
KW - inherited genetic mutations
KW - malignant mesothelioma
KW - single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85086753076&partnerID=8YFLogxK
U2 - 10.3390/ijms21124327
DO - 10.3390/ijms21124327
M3 - Review article
C2 - 32560575
AN - SCOPUS:85086753076
SN - 1661-6596
VL - 21
SP - 1
EP - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
M1 - 4327
ER -