Genetic predisposition for malignant mesothelioma: a concise review

Publication date: Available online 6 March 2019Source: Mutation Research/Reviews in Mutation ResearchAuthor(s): Marta Betti, Anna Aspesi, Marika Sculco, Giuseppe Matullo, Corrado Magnani, Irma DianzaniAbstractMalignant 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 predispos...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research