Genetic predisposition for malignant mesothelioma: A concise review

Anno:

2019

Genetic predisposition for malignant mesothelioma: A concise review

Betti M1, Aspesi A2, Sculco M1, Matullo G3, Magnani C4, Dianzani I1

Mutat Res. 2019 Jul - Sep;781:1-10. doi: 10.1016/j.mrrev.2019.03.001. Epub 2019 Mar 6. PMID: 31416570

Author information

Department of Health Sciences, Università del Piemonte Orientale, via Solaroli 17, 28100 Novara, Italy.
Department of Health Sciences, Università del Piemonte Orientale, via Solaroli 17, 28100 Novara, Italy. Electronic address: anna.aspesi@med.uniupo.it.
Department of Medical Sciences, Università degli Studi di Torino e Unità di Genetica Medica, AOU Città della Salute e della Scienza, 10126 Turin, Italy.
Department of Translational Medicine, Università del Piemonte Orientale, SSD Epidemiologia dei Tumori, AOU Maggiore della Carità e CPO-Piemonte, via Solaroli 17, 28100 Novara, Italy.

Abstract

Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.