Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.

The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.

[Death certification of pleural malignant mesothelioma from the Italian National Institute of Statistics: a comparison on 269 clinical diagnosis confirmed at autopsy (1997-2016)]. / La certificazione Istat di decesso per mesotelioma maligno pleurico: comparazione con 269 diagnosi cliniche confermate all'autopsia (1997-2016).

OBJECTIVES: To evaluate the agreement between pleural malignant mesothelioma diagnosis in life, with diagnoses confirmed at autopsy, and the certification of the cause of death in the form of the Italian National Institute of Statistics (Istat). DESIGN: comparison between autopsic cases and cases from Istat. SETTING AND PARTICIPANTS: two series of autopsy diagnoses of pleural malignant mesothelioma placed from 1997 to 2016; 185 in shipyard workers and 90 in Brescia province inhabitants, for whom the Istat death form was acquired for 180 and 89 subjects, respectively. RESULTS: the general agreement between pleural malignant mesothelioma clinical diagnosis in life and death certification was about 91% for the first group and 92% for the second one. In the first group, the age at diagnosis does not affect the accuracy of the death certification, which instead increased over time to become total in the period 2010-2016. CONCLUSIONS: the study suggests that the agreement between pleural malignant mesothelioma clinical diagnosis and certification of the cause of death appears to be very high.

Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure.

BACKGROUND: Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited. OBJECTIVES: To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure. METHODS: We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD). RESULTS: GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases. CONCLUSIONS: Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.