Domenica Cavone

Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register.

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 = 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.

A cluster of familial malignant mesothelioma with del(9p) as the sole chromosomal anomaly

We describe a family of three sisters affected by malignant mesothelioma (MM) (2 pleural and 1 peritoneal) and one brother affected by pleural plaques. All members of the family had been subjected to previous asbestos exposure of environmental-residential type. For 13 years, from 1951 to 1964, their housing was provided by the fathers employer, an asbestos cement factory, and the factory warehouse was on the ground floor of the building they lived in. DNA extracted from paraffin-embedded MM samples was used to search for chromosomal alterations by a comparative genomic hybridization (CGH) method. In two cases, a loss at 9p was found to be the only change. The loss at 9p is a frequent event in malignant mesothelioma and the fact that this anomaly was diagnosed in two sisters as the only alteration suggests that this region may be the site of one or more oncosuppressor genes that could play an important role in the development of MM and in inducing greater genetic susceptibility to the carcinogenic effects of asbestos.

Non-occupational exposure to asbestos and malignant mesothelioma in the Italian National Registry of Mesotheliomas

Background Malignant mesotheliomas are strictly related to asbestos, but in a proportion of cases no exposure can be recalled. Published estimates of this proportion have important variations. Historical and geographical differences in the fraction of cancer due to any given exposure are to be expected, but incomplete identification of non-occupational exposures may have played a role. Methods To assess the role of non-occupational exposures in causing malignant mesotheliomas in Italy, the exposures of cases registered by the national mesothelioma registry (ReNaM) were examined. ReNaM started in 1993 in five regions and currently covers 98% of the Italian population. Information on occupational and non-occupational exposures of cases is collected whenever possible. Results From 1993 to 2001 ReNaM registered 5173 malignant mesothelioma cases, and exposures were assessed in 3552 of them. 144 and 150 cases with exposures limited to environmental (living in the neighbourhood of an industrial or natural source of asbestos) or familial (living with a person occupationally exposed to asbestos) circumstances, respectively, were identified, accounting for 8.3% of all cases. Conclusions Geographical variations in the proportion of cases due to non-occupational exposures may be explained by the past distribution of asbestos-using industries.

Asbestos Fibre Burden in the Lungs of Patients with Mesothelioma Who Lived Near Asbestos-Cement Factories

BACKGROUND Epidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants. OBJECTIVES To provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients. METHODS We analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay. RESULTS The lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos. CONCLUSIONS Environmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.

Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register

Objectives The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM). Methods ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed. Results Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearsons r coefficient, p<0.001). Modalities of exposure to asbestos fibres were investigated for 392 cases. Conclusions The rarity of the disease, the low specificity of diagnosis and difficulties in identifying the modalities of asbestos exposure call for caution in discussing aetiological factors other than asbestos.

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues

Introduction 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. Methods The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Results Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100 000) for men and 1.45 for women, respectively. Among the 15 845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12 065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Conclusions Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

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.

Seroprevalence of Q-fever, brucellosis and leptospirosis in farmers and agricultural workers in Bari, southern Italy

To establish the seroprevalence of antibodies to C. burnetii, Leptospira and Brucella in subjects at risk of exposure, 128 workers exposed to farm animals and 280 healthy blood donors were studied. Antibodies to C. burnetii, Leptospira and Brucel- la were determined by indirect immunofluorescence assay, by microagglutination test (MAT) and by standard tube agglutination test, respectively. Of subjects exposed to farm animals 73.4% were positive for anti C. burnetii IgG (titer ≥ 20) compared to 13.6% of control subjects (p < 0.0001). The seroprevalence was found mainly among the veterinar- ians (100%) and the animal breeding workers (84%). The trend of percentage of positiv- ity to antibodies to C. burnetii is significant only in the group of workers ≥ 70 years, when adjusted for sex and occupation. None of the subjects examined had antibodies to Leptospira and Brucella. Further improvements in the occupational hygiene of the work environment is advisable.

The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure

Introduction The 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. Methods Incident 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. Results In 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. Conclusions The 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.

Assessment of environmental and occupational exposure to heavy metals in Taranto and other provinces of Southern Italy by means of scalp hair analysis

The monitoring of heavy metals in industrialized areas to study their association with different occupational and environmental factors is carried out in different ways. In this study, scalp hair analysis was used for the assessment of exposure to these metals in the industrial city of Taranto, characterized by a severe environmental pollution. The highest median values were observed for aluminum, barium, cadmium, lead, mercury, and uranium. Moreover, in the industrial area of Taranto, high levels of barium, cadmium, lead, mercury, nickel, and silver were observed in comparison with other Apulia areas. The risk odds ratios (ORs) for observing values above the 50th percentile were elevated for mercury and fish consumption, uranium and milk consumption, lead and female sex, and aluminum and mineral water consumption. No significant increased risk was observed for occupational activities. In a dendrogram of a cluster analysis, three clusters were observed for the different areas of Taranto (Borgo, San Vito, and Statte). A scree plot and score variables plot underline the presence of two principal components: the first regarding antimony, lead, tin, aluminum and silver; the second regarding mercury and uranium. The observed clusters (Borgo, San Vito, and Statte) showed that lead, antimony, tin, aluminum, and silver were the main component. The highest values above the 50th percentile of these minerals, especially lead, were observed in the Borgo area. The observed metal concentration in the Borgo area is compatible with the presence in Taranto of a military dockyard and a reported increase of lung cancer risk among residents of that area.