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Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N 5 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as ''at risk'' (asbestos-cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.Key words: asbestos, mesothelioma, pleural, national register, Italy ReNaM Working Group: Massari S., Branchi C.; Detragiache E.; Merletti F., Gangemi M., Stura A., Brentisci C., Cammarieri Diglio G., Macerata V., Gilardetti M.; Lazzarotto A., Benfatto L., Bianchelli M., Mazzucco G.; Sieno C., Pesatori A.C.; Gioffrè F., Bressan V.; De Michieli P.; Mangone L., Storchi C.; Seniori Costantini A., Badiali A.M., Cacciarini V., Giovannetti L., Martini A.; Calisti R.; La Rosa F., Stracci F., D'Alò D.; Perucci C.A., Forastiere F., Cavariani F., Ascoli V., Sangalli M.; Trafficante L., Gatta S.; Menegozzo M., Izzo F., Canfora M.L., Santoro M., Viscardi F.; Massaro T.; Convertini L.; Leotta A., Lio S.G.; Dardanoni G., Scondotto S.; Corrias G.A., Angius M.R., Nieddu V.

BackgroundMalignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE).Methodology/Principal findingsWe investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87–1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13–1.13) and of 0.51 (95%CI 0.17–1.52) for miR-30e-3p.ConclusionsThis study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.

BackgroundPrevious ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).MethodsIn the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster.ResultsThirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters.ConclusionsOur study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1301-2) contains supplementary material, which is available to authorized users.

Few studies have examined the incidence of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure (occupational, familial, or environmental). We assessed the impact of asbestos exposure-global and by source-on the incidence of MM in Broni, an Italian town in which an asbestos cement factory once operated . Based on data collected by the Regional Mesothelioma Registry, we calculated the number of observed and expected MM cases among workers, their cohabitants, and people living in the area in 2000-2011. We identified 146 MM cases (12.57 expected), 138 pleural and eight peritoneal, attributable to exposure to asbestos from the factory. Thirty-six cases had past occupational exposure at the factory (0.64 expected), numbering 30 men (25 pleural, five peritoneal) and six women (four pleural, two peritoneal). In the families of the workers, there were 37 MM cases (3.03 expected), numbering five men (all pleural) and 32 women (31 pleural, one peritoneal). Among residents in Broni or the surrounding towns, there were 73 cases of pleural MM (8.90 expected), numbering 24 men and 49 women. The largest MM excess was found in the towns of Broni (47 observed, 3.02 expected) and Stradella (16 observed, 1.51 expected). This study documents the large impact of the asbestos cement factory, with about 133 excess MM cases. The largest MM burden was among women, from non-occupational exposure. Almost half of the MM cases were attributable to environmental exposure. Dear Editor of Environment International, we are submitting a manuscript on the impact of asbestos exposure, related to an asbestoscement factory, on mesothelioma incidence in a community in northern Italy. Differently from previous works, we were able (thanks to a mesothelioma registry operating in the region), to evaluate the global impact on workers, their family members, and the rest of the population. We found a large overall impact of asbestos exposure, with over 130 excess cases in 12 years. Moreover, the largest burden was in women, and environmental exposure accounted for half of the cases.Continuous documentation of the effects of asbestos exposure also outside the occupational context is important not only for local communities, but also to increase awareness of the health effects of asbestos in countries that still use it and in which the perception of the real entity of health effects attributable to asbestos is still poor.We assure that the manuscript is an original work, has not been previously published whole or in part, and is not under consideration for publication elsewhere.None of the authors have any actual or potential competing financial interests regarding the submitted article.All authors have read the manuscript, agree the work is ready for submission to a journal, and accept responsibility for the manuscript's contents.

IntroductionThe epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.MethodsIncident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.ResultsIn the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.ConclusionsThe consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.

ObjectivesIn Italy, asbestos has been extensively used from 1945 to 1992. We evaluated the impact of exposure to asbestos on occurrence of malignant mesothelioma (MM) in the Lombardy Region, Northwest Italy, the most populated and industrialised Italian region.MethodsFrom the Lombardy Mesothelioma Registry, we selected all incident cases of MM diagnosed between 2000 and 2012. We described sources of exposure to asbestos and examined time trends of MM rates. Using Poisson age-cohort models, we derived projections of burden of MM in the Lombardy population for the period 2013–2029.ResultsIn 2000–2012, we recorded 4442 cases of MM (2850 men, 1592 women). Occupational exposure to asbestos was more frequent in men (73.6%) than in women (38.2%). Non-occupational exposure was found for 13.6% of women and 3.6% of men. The average number of cases of MM per year was still increasing (+3.6% in men, +3.3% in women). Incidence rates were still increasing in individuals aged 65+ years and declining in younger people. A maximum of 417 cases of MM (267 men, 150 women) are expected in 2019. We forecast there will be 6832 more cases (4397 in men, 2435 in women) in the period 2013–2029, for a total of 11 274 cases of MM (7247 in men, 4027 in women) in 30 years.ConclusionsThis study documented a high burden of MM in both genders in the Lombardy Region, reflecting extensive occupational (mainly in men) and non-occupational (mainly in women) exposure to asbestos in the past. Incidence rates are still increasing; a downturn in occurrence of MM is expected to occur after 2019.

Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160 000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure