1. Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes
- Author
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Paolo Bironzo, Milena Rondón-Lagos, Francesca Vignolo Lutati, Roberta Libener, Dario Mirabelli, Anna Aspesi, Barbara Pasini, Giorgio V. Scagliotti, Michele Valiante, Daniela Ferrante, Federica Grosso, Antonella Maffè, Giuseppe Matullo, Paola Savoia, Paola Ogliara, Irma Dianzani, Marta Betti, Marika Sculco, Silvana Ungari, Renzo Boldorini, Luisella Righi, Corrado Magnani, C. Laura Gironi, Francesca Napoli, and Elisabetta Casalone
- Subjects
0301 basic medicine ,Adult ,Male ,Mesothelioma ,Cancer Research ,Tumor suppressor gene ,DNA Repair ,BAP1 ,BAP1-TPDS ,cumulative asbestos exposure ,DNA repair genes ,germline variants ,mesothelioma ,Asbestos ,Cohort Studies ,Environmental Exposure ,Female ,Genetic Predisposition to Disease ,Germ-Line Mutation ,Humans ,Italy ,Middle Aged ,Tumor Suppressor Proteins ,Ubiquitin Thiolesterase ,Genetics ,Biology ,Germline ,Cancer syndrome ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,CDKN2A ,medicine ,Environmental exposure ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research - Abstract
Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.
- Published
- 2018