Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy)



Caterina BrunoI; Rosario TuminoII; Lucia FazzoI; Giuseppe CasconeII; Achille CernigliaroIII; Marco De SantisI; Maria Concetta GiurdanellaII; Carmela NicitaII; Patrizia Concetta RolloII; Salvatore ScondottoIII; Eugenia SpataII; Amerigo ZonaI; Pietro CombaI

IDipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Rome, Italy
IIRegistro Tumori, Dipartimento di Prevenzione Medica, ASP Ragusa, Ragusa, Italy
IIIDipartimento Attività Sanitarie e Osservatorio Epidemiologico, Regione Sicilia, Palermo, Italy

Address for correspondence




INTRODUCTION. Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite.
MATERIALS AND METHODS. Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants.
RESULTS. The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50.
DISCUSSION AND CONCLUSIONS. Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.

Key words: fluoro-edenite. pleural mesothelioma. peritoneal mesothelioma. prevention




In the frame of the national programme of epidemiological surveillance of mortality from malignant pleural neoplasms (MPN), a proxy of pleural mesothelioma incidence, conducted by Istituto Superiore di Sanità (ISS), with reference to the time-window 1988-92, an excess risk based on four observed death versus 0.9 expected was reported in the town of Biancavilla, located in the Province of Catania (Sicily), at the slopes of the Etna volcano. Although based on a small number of cases, the excess was regarded as statistically significant since the lower limit of the confidence interval was greater than one, and thus Biancavilla was included in the list of Italian municipalities at risk of mesothelioma, where assessment of asbestos exposure was recommended [1]. The Major and the local health authorities initially challenged this inclusion, since they could easily certify that no relevant asbestos exposure occurred in that town of about 20 000 inhabitants where orange and lemon growing

were the prevailing economic activities. It was anyway agreed to check if further deaths from mesothelioma had been reported, if cases were hystologically confirmed and if they had been occupationally exposed to asbestos; in about one year time (1997 and beginning of 1998) it was ascertained that further cases had been reported also between 1993 and 1997, that most of them were hystologically confirmed and that no consistent occupational exposure to asbestos was detected. Concurrently, asbestos fibres were searched in the neighbouring stone quarry of Monte Calvario where material employed in the local building industry was caved. This investigation lead to the finding of an amphibolic fibre occurring in the relatively soft material located in-between lavic rocks; that soft stone material was extensively used to produce sand, cement and plaster. Based on these results, in May 1998 the Director of the ISS wrote to the Sicilian Regional Government, to the Major of Biancavilla and to the local health authorities recommending to terminate quarrying activities in Monte Calvario, to remove building material by-products present near newly-constructed houses and to cover with asphalt all roads previously paved with Monte Calvario quarry waste material [2]. A detailed report on these activities was then published [3].

The Biancavilla fibre was initially regarded as an intermediate mineralogical phase between tremolite and actinolite [3]. In the meanwhile, though, a series of investigations performed by Gianfagna and coworkers lead to the identification of a new amphibole endmember, fluoro-edenite [4, 5] as extensively discussed by Bruni et al. in this same issue [6].

The environmental remediation process started in 2002, with the official recognition of Biancavilla as a National Priority Contaminated Site, as discussed by Bruni et al. [6] in this same issue. Being aware that this decision would provide in the long run a major contribution to risk-reduction in Biancavilla, epidemiologists from ISS together with colleagues from other institutions designed and realized some further studies aimed at pursuing a better insight in the health impact of environmental exposure to fibres with fluoro-edenitic composition. The main steps of this second phase of investigations can be summarized as follows.

Biggeri et al. [7] performed a geographic mortality study in all 36 municipalities located in the volcanic area of Mount Etna, in order to investigate the association between chronic obstructive pulmonary disease (a nosological entity in which cases of unrecognized lung fibrosis, if present, might have been allocated) and pleural mesothelioma. The association was observed, especially among women, after adjustment for urbanrural gradient and lung cancer mortality, thus suggesting an etiological role of fluoro-edenite exposure in the occurrence of non-malignant respiratory disease. Putzu et al. [8] performed a pilot study on the determination of fibres in the sputum of chronic bronchitis patients resident in Biancavilla as an indicator of exposure to fluoro-edenite; preliminary findings showed that six out of twelve subjects had at least one of three samples positive for fluoro-edenite. Bruno et al. [9] through a collaborative work with Sicilian Region Mesothelioma Registry, provided the first estimate of mesothelioma incidence in Biancavilla (5.4 x 100 000). This figure is about 10 times higher than the Sicilian incidence rate. For detailed review and critical discussion of this set of studies, the reader is referred to Bruno et al. [10].

The purpose of the present paper is to update the previous incidence study and to review the complete case-serie of mesothelioma cases (1988-2011), with the aim of achieving a better insight in the characteristics of fluoro-edenite induced mesothelioma.



Biancavilla malignant mesothelioma case series

In 1997 ISS, together with Catania Local Health Unit, collected Biancavilla malignant mesothelioma cases through municipality mortality Registrar, family doctors and hospital records. If available, histology slides were collected and reviewed by a single expert pathologist. Information about clinical history, occupation, relevant behaviour and residential history were

collected by Local Health Unit physicians through the subjects (if alive) or, in most cases, through next-of-kins. Since 1998, mesothelioma incidence in Biancavilla and previous exposures of registered cases have been taken in charge by the Sicilian Operative Regional Centre (COR) of the National Mesothelioma Registry (ReNaM), a nation-wide system for malignant mesothelioma monitoring. Information have been collected through a structured questionnaire by trained interviewers.

ReNaM classifies mesotheliomas by level of diagnostic certainty:

1. "certain malignant mesothelioma" characterized by the following condition: microscopic examination on material (histological or cytological with centrifugation of the sediment) enclosed in paraffin, with characteristic morphological pattern

(1.1) with immunohistochemistry or

(1.2) immunohistochemistry not carried out or not defined;

2. "probable malignant mesothelioma"

(2.1) with histological or cytological examination with enclosure in paraffin carried out, but which did not give a result indicating mesothelioma in a clear and reliable way (doubtful case) or

(2.2) with cytological examination not enclosed in paraffin, with characteristic pattern and report expressed in terms clearly indicative of mesothelioma;

3. "possible malignant mesothelioma"

(3.1) characterized by indicative clinical and radiolog ical data with diagnosis of discharge of mesothelioma or

(3.2) Death Certificate Only (DCO) with presence on the death certificate of the term "mesothelioma".

Asbestos exposure has been assessed and codified according to the ReNaM criteria which comprises three levels of certainty of occupational exposure (1. certain, 2. probable, 3. possible); three other modalities of exposure (4. household exposure, 5. environmental exposure, 6. non-professional exposure during leisure time activities). Other endpoints can be: 7. unlikely exposure, 8. unknown exposure (incomplete and insufficient information), 9. exposure definition in progress; 10. unclassified exposure (no information is available nor will presumably be available).

Biancavilla malignant mesothelioma incidence

Malignant mesothelioma incidence in Biancavilla municipality was compared to the regional incidence rates. Standardized Incidence Ratios (SIRs), with their 95% Confidence Intervals (95% CI) were computed, by applying the indirect standardization method by use of STATA software. For the computation of the Sicilian Region incidence rates, the population and cases resident in Biancavilla municipality were excluded. SIRs were computed for total malignant mesothelioma, pleural and peritoneal mesothelioma, in the two genders, separately. Data source for cases was the Sicilian Operative Regional Centre (COR) of the National Mesothelioma Registry. All cases diagnosed between 01/01/1998 through 31/12/2011, resident in Biancavilla at time of diagnosis, and classified as "certain", "probable" or "possible" were eligible for the study. At 05/03/2014, 24 pleural mesotheliomas and two peritoneal mesotheliomas were collected in the COR database.



Biancavilla malignant mesothelioma case series

Since 1988 to the end of 2011 45 cases of mesothelioma were detected among Biancavilla residents. Before 1998 a total of 17 cases of pleural mesothelioma had been collected by ISS researchers and Local Health Unit physicians (Table 1). For nine cases out of 17, histology slides were found and were available to be reviewed by an experienced pathologist: all diagnoses were confirmed. No certain occupational exposure to asbestos fibres was detected in any case, two subjects had been employed for a short time in industrial sectors in which asbestos might have been used. All cases but one were long-time residents in Biancavilla and eleven of them always resided in the town.

Since 1998 Sicilian COR has taken charge of the investigation on Biancavilla mesotheliomas, using standardized procedures, questionnaires and classifications [11]. Between 1998 and 2011, 28 mesothelioma cases were detected, even if two of them were not eligible to be included in the Biancavilla COR cases as they were not resident there at time of diagnosis (Table 2). In eight cases, only environmental exposure to Biancavilla fibres was ascertained, and an investigation to identify a concurrent occupational or non occupational exposure to asbestos fibres outside Biancavilla, if any, is ongoing for eleven cases. No one experienced a certain professional exposure to asbestos, one subject worked in an industrial sector in which asbestos had been used, and three subjects worked in industrial sectors in which asbestos presence could occur. Incomplete and insufficient information (unknown exposure), were collected for two more subjects, even if one of them, a farmer, experienced working in the quarry as a temporary job.

Finally, one case refused to be interviewed (information not available). All cases were long-time resident in Biancavilla and all but five always resided there.

Twenty-six mesothelioma cases were diagnosed in subjects resident in the municipality of Biancavilla at time of diagnosis and collected by COR, 13 in men and 13 in women. In two of them, one male and one female, peritoneum was affected, the other mesotheliomas were localized in the pleura. Mean age at diagnosis was about 60 in men and 70 in women (Table 3). The difference between mean age in men and women was noticeable, in particular for pleural mesothelioma. The subjects with peritoneal mesothelioma, one man and one woman, were respectively 63 and 65 years old.



Biancavilla mesothelioma incidence

Table 4 clearly shows that the Standardized Incidence Ratios (SIRs) for mesothelioma in Biancavilla were steadily high: the overall SIR was 5.76 (95% CI 3.768.44) respectively, 3.69 (95% CI 1.97-6.32) in men and (95% CI 6.97-22.00) in women. An increased risk of pleural mesothelioma was also demonstrated (Overall SIR 5.65, 95% CI 3.62-8.41), both in men (SIR 3.63, 95% CI 1.87-6.34), and in women (SIR 12.75, 95% CI 6.59-22.00). The highest overall SIR was found for peritoneal cases (SIR 7.92, 95% CI 0.96-20.00), based on two observed cases.



With regard to pleural mesothelioma, when SIR estimates were stratified by age (Table 5), extremely high figures were shown in the younger age groups: the overall SIR in subjects less than 50 years old was 21.34 (95% CI 6.93-50 00) (four cases in men and one in a woman). These findings were strengthened by the results in the less than 40 years age group (overall SIR 62.88, 95% CI 13.00-180.00, 3 cases).



These findings are consistent with a strong excess of mesothelioma incidence among Biancavilla inhabitants in the absence of known occupational sources of asbestos exposure.

The cases sex ratio was 1:1, the Standardized Incidence Ratio was elevated in men and even more elevated in women. It is also important to note that a ten years lower mean age at diagnosis was experienced by the male population and to remark the extremely high SIR in the younger age groups.



The Italian National Mesothelioma Registry was created to establish a nation-wide system for malignant mesothelioma monitoring because of the massive utilization of asbestos which took place in Italy, followed by a severe health impact. ReNaM objectives are in particular centred on estimating mesothelioma incidence in Italy, and on contributing to the assessment of the effects of industrial use of asbestos and to the identification of sources of asbestos exposure; however environmental exposures to asbestos fibres have been investigated as well. In the present study, the same methodology has been used to identify or exclude occupational exposures to asbestos in Biancavilla resident cases of mesothelioma, while the definition of "environmental exposure" refers to fibres with fluoro-edenitic composition.

In vitro studies showed that fibres with fluoro-edenitic composition behave similarly to crocidolite, as discussed by Balan et al. in this issue [12], human lung carcinoma cells have been exposed to two different materials: prismatic fluoro-edenite and fibres with fluoroedenitic composition. Only in the second case, they exhibit features typical of transformed cells. Most of the results for fibres with fluoro-edenitic composition were comparable to those obtained with crocidolite, used as a "positive control". Accordingly, in vivo studies demonstrated that the fluoro-edenitic composition fibre sample induces mesotheliomas [13].

Malignant mesothelioma (MM) incidence rates have been reported to be 1.2-9 times higher among men than among women because of occupational exposures [14]. Besides occupational settings, MM is also associated with domestic exposure in family members of asbestos workers [15]. The role of environmental exposure [16, 17] related to asbestos factories, mines, or naturally occurring asbestos (NOA) has been investigated in Greece, [18], Cyprus [19], Turkey [20-24], Corsica [25, 26], Italy [27], California, US [28], Libby, Montana, US [29] and China [30].

The sex ratio of about 1:1 both in our previous studies [3, 9] and in this issue corroborates the hypothesis of an environmental exposition rather than an occupational source of asbestos exposure. In Cappadocia, Turkey, a very high incidence of pleural mesothelioma in three villages was found at the end of the 1970s. From 1970 to 1987, 108 cases of pleural mesothelioma were identified, and an annual incidence of more than 8,000 cases/million was calculated. The incidence was identical for men and women (the ratio M/W ranged between one and two), and the mean age was roughly 50, with a range of 26 to 75 years [31]. These cases of MM were caused by exposure to erionite fibers, which are not NOA, being fibrous zeolites [32]. Baris and Grandjean [33] confirmed this high incidence. Erionite fibers in pulmonary biopsy and sputum samples from mesothelioma patients were found [34, 35]. In Biancavilla six out of twelve subjects had samples positive for fluoroedenitic fibres in the sputum [8].

In New Caledonia an excess incidence of MM was identified in a period of 10 years (1978-1987) [36]. In the same region, Baumann et al. [37], studying 109 MM cases recorded between 1984 and 2008, found in the Houaïlou area, where an important asbestos mining activity was located during the 1960s-1970s, a world age-standardized rate of 128.7 per 100 000 per son-years [95% confidence interval (CI) 70.41-137.84]. They evaluated the presence of serpentinite on roads as a major environmental risk factor for mesothelioma. In a case-control study conducted in the province of Sivas, Turkey, Bayram et al. [38] demonstrated a quantitative relationship between the risk of either malignant or non malignant pleural diseases and the proximity of the residence at birth to ophiolites, rocks known as sources of NOA.

The Biancavilla population showed excesses for pleural mesothelioma in mortality and in hospital discharges and non malignant respiratory diseases such as chronic respiratory diseases (in women) and only for hospital discharges from all respiratory diseases and in particular pneumoconiosis [39]. Diseases of circulatory system showed excess mortality among both genders.

As regards the occurrence in Biancavilla of MM cases in young people this finding is consistent with Baris et al. [31] findings concerning subjects exposed to erionite. In our study even the figures (four cases out 45 aged less than 40 years old, two of them in their late twenties) are surprisingly high: it needs to be considered for example that, in Australia, in 2008 out of 543 men diagnosed with mesothelioma there was only one man in his early thirties but none younger, and similarly out of 118 women diagnosed with mesothelioma there was only one woman aged in her early thirties but none younger [40].

Latency period for most of malignant mesothelioma of occupational origin is considered to be in a range between 20 to 40 years: in a review of 21 articles by Lanphear & Buncher [41] 96% had a latent period of at least 20 years and the estimated median latent period was at least 32 years after the initial exposure. Latency periods were examined in 312 cases of malignant pleural mesothelioma, diagnosed in the Trieste-Monfalcone area, Italy [42]; they ranged from 14 to 72 years (mean 48.7, median 51). Latency time analysis for 2544 cases diagnosed during the period 1993-2001 and eligible for the analysis was performed by ReNaM [43]. Median latency was 44.6 years (95% CI 44.1-45.0). Latency increased constantly during the observed period with respect to the year of diagnosis: estimated mean latency period among pleural MM cases diagnosed in 1993 and in 2001 was 41.7 and 46.2 years, respectively. In the hypothesis of an asbestos-like behaviour of the Biancavilla fibres with fluoro-edenitic composition, exposure to fibres had to occur about 30 years before the mesothelioma outbreak.

The latency period of mesothelioma in fibres with fluoro-edenitic composition has not been studied yet; if it was similar to the latency of asbestos exposed mesothelioma cases, the occurrence of pleural MM in young adults would require exposure in childhood or in teenage years. Conti et al. [39] in this issue showed that the mortality for malignant pleural neoplasms under 50 concerns Biancavilla and two neighbouring communities.

The disparity of ten years in mean age at diagnosis in men and in women in pleural MM observed in Biancavilla cases and the occurrence of more male cases in younger ages have to be investigated taking into account the source population, as recommended by Consonni [44]. The possible role of fibre exposure associated to outdoor recreational activities should be assessed in this frame.

This study is the first report of an excess incidence of peritoneal mesothelioma in Biancavilla, even if based on two cases; this finding in noteworthy in view of the induction of peritoneal mesothelioma in rats after intraperitoneal administration of fibres with fluoro-edenitic composition that was reported by Soffritti et al. [13].

An analysis of different behaviours in Biancavilla adults and children in their everyday lives could be useful to figure out the way to reduce fibres exposures.



In light of the evidence that was illustrated and discussed in the present paper, some conclusions appear to be warranted.

The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50.

Analysis of individual data shows that the contribution of asbestos exposure to this localized high occurrence of mesothelioma is substantially irrelevant.

Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite.

Environmental exposure to fibres with fluoro-edenitic composition appears to be the causally related to the elevated mesothelioma occurrence in Biancavilla.

In this frame, environmental clean-up is the main goal to be pursued in public health terms.

A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected investigations concerning, namely:

  • the incidence of new cases and an in-depth collection of their occupational, residential and life style histories;
  • mortality and hospitalization, also in order to evaluate their temporal trends;
  • mean age of mesothelioma cases in relation to the population characteristics;
  • health condition profile of residents in Biancavilla to elucidate the characteristics of non neoplastic effects on respiratory system (functionality and imaging) and to study the cardiovascular diseases [39];
  • investigation on modality of exposures in the environmental context in the everyday lives of adults and children [6].

The authors also recommend to adopt guidelines and rules in building sector and soil materials handling to minimize fibre dispersion.


Conflict of interest statement

There are no potential conflicts of interest or any financial or personal relationships with other people or organizations that could inappropriately bias conduct and findings of this study.



1. Di Paola M, Mastrantonio M, Carboni M, Belli S, Grignoli M, Comba P, Nesti M. Mortality from malignant pleural neoplasms in Italy in the years 1988-1992. Roma: Istituto Superiore di Sanità; 1996. (Rapporti ISTISAN, 96/40).         

2. Donelli G, Marsili D, Comba P. Le problematiche scientifico-sanitarie correlata all'amianto: l'attività dell'Istituto Superiore di Sanità negli anni 1980-2012. I beni storici e scientifici dell'Istituto Superiore di Sanità. 2012. Istituto Superiore di Sanità. Quaderno 9. p. 67. Available from:        

3. Paoletti L, Batisti D, Bruno C, Di Paola M, Gianfagna A, Mastrantonio M, Nesti M, Comba P. Unusually high incidence of malignant pleural mesothelioma in a town of eastern Sicily: an epidemiological and environmental study. Arch Environ Health 2000;55:392-98. DOI: 10.1080/00039890009604036        

4. Gianfagna A, Oberti R. Fluoro-edenite from Biancavilla (Catania, Sicily, Italy): crystal chemistry of a new amphibole end-member. Am Mineral 2001;86:1489-93.         

5. Comba P, Gianfagna A, Paoletti L. Pleural mesothelioma cases in Biancavilla are related to a new fluoro-edenite fibrous amphibole. Arch Environ Health 2003;58(4):229 32. DOI: 10.3200/AEOH.58.4.229-232        

6. Bruni BM, Soggiu ME, Marsili G, Brancato A, Inglessis M, Palumbo L, Piccardi A, Beccaloni E, Falleni F, Mazziotti Tagliani S, Pacella A. Environmental concentrations of fibers with fluoro-edenitic composition and population exposure in Biancavilla. Ann Ist Super Sanità 2014;50:119-26        

7. Biggeri A, Pasetto R, Belli S, Bruno C, Di Maria G, Mastrantonio M, Trinca S, Uccelli R, Comba P. Mortality from chronic obstructive pulmonary disease and pleural mesothelioma in an area contaminated by natural fiber (fluoro-edenite). Scand J Work Environ Health 2004;30(3):249-52. DOI: 10.5271/sjweh.786        

8. Putzu MG, Bruno C, Zona A, Massiccio M, Pasetto R, Piolatto PG, Comba P. Fluoro-edenitic fibres in the sputum of subjects from Biancavilla (Sicily): a pilot study. Environ Health 2006;(16)5:20. DOI: 10.1186/1476-069X-5-20        

9. Bruno C, Belli S, Cernigliaro A, Cossari P, Pennisi P, Scondotto S, Tumino R, Nicita C, Zona A, Comba P. An estimate of pleural mesothelioma incidence in Biancavilla, Sicily, Italy, 1998-2004. Eur J Oncol 2007;12:183-87.         

10. Bruno C, Comba P, Zona A. Adverse health effects of fluoro-edenitic fibres: epidemiologic evidence and public health priorities. In: Mehlman MA, Soffritti M, Landrigan P, Bingham E, Belpoggi F (Ed.). Living in a chemical world: framing the future in light of the past. Ann NY Acad Sci 2006;1076:778-83.         

11. INAIL ex-ISPESL. National Mesothelioma Register (Article 36, n°277/91 – Dpcm 308/02) Guidelines for the identification and definition of malignant mesothelioma cases and the transmission to ISPESL by Regional Operating Centres (2010). Available from:        

12. Balan G, Del Brocco A, Loizzo S, Fabbri A, Maroccia Z, Fiorentini C, Travaglione S. Mode of action of fibrous amphiboles: the case of Biancavilla (Sicily, Italy). Ann Ist Super Sanità 2014;50:133-8.         

13. Soffritti M, Minardi F, Bua L, Degli Esposti D, Belpoggi F. First experimental evidence of peritoneal and pleural mesotheliomas induced by fluoro-edenite fibres present in Etnean volcanic material from Biancavilla (Sicily, Italy). Eur J Oncol 2004;9(3):169-75.         

14. Ross D, McDonald JC. Occupational and geographical factors in the epidemiology of malignant mesothelioma. Monaldi Arch Chest Dis 1995;50:459-63.         

15. Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C. Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. Environ Health Perspect 2007;115:1401-5. DOI: 10.1289/ehp.10195        

16. Hillerdal G. Mesothelioma: cases associated with nonoccupational and low dose exposures. Occup Environ Med 1999;56:505-13. DOI: 10.1136/oem.56.8.505        

17. Maule MM, Magnani C, Dalmasso P, Mirabelli D, Merletti F, Biggeri A. Modeling mesothelioma risk associated with environmental asbestos exposure. Environ Health Perspect 2007;115:1066-71. DOI: 10.1289/ehp.9900        

18. Constantopoulos SH, Malamou-Mitsi V, Goudevenos J, Papathanasiou MP, Pavlidis NA, Papadimitriou CS. High incidence of malignant pleural mesothelioma in neighbouring villages of North-Western Greece. Respiration 1987;51:266-71. DOI: 10.1159/000195212        

19. McConnochie K, Simonato L, Mavrides P, Christofides P, Pooley FD, Wagner JC. Mesothelioma in Cyprus: the role of tremolite. Thorax 1987;42:342-7. DOI: 10.1136/ thx.42.5.342        

20. Carbone M, Emri S, Dogan A, Steele I, Tuncer M, Pass H, et al. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nat Rev Cancer 2007;7:147-54. DOI: 10.1038/nrc2068        

21. Metintas S, Metintas M, Ucgun I, Oner U. Malignant mesothelioma due to environmental exposure to asbestos: follow-up of a Turkish cohort living in a rural area. Chest 2002;122(6):2224-9. DOI: 10.1378/chest.122.6.2224        

22. Metintas M, Metintas S, Ak G, Erginel S, Alatas F, Kurt E, Ucgun I, Yildirim H. Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposure. Respirology 2008;13(1):117-21. DOI: 10.1111/j.1440-1843.2007.01187.x        

23. Senyigit A, Dalgic A, Kavak O, Tanrikulu AC. Determination of environmental exposure to asbestos (tremolite) and mesothelioma risks in the southeastern region of Turkey. Arch Environ Health 2004;59(12):658-62. DOI: 10.1080/00039890409602950        

24. Dumortier P, Coplü L, de Maertelaer V, Emri S, Baris I, De Vuyst P. Assessment of environmental asbestos exposure in Turkey by bronchoalveolar lavage. Am J Respir Crit Care Med 1998;158(6):1815-24. DOI: 10.1164/ajrccm.158.6.9712119        

25. Rey F, Boutin C, Steinbauer J, et al. Environmental pleural plaques in an asbestos exposed population of northeast Corsica. Eur Respir J 1993;6(7):978-82.         

26. Rey F, Viallat JR, Boutin C, Farisse P, Billon-Galland MA, Hereng P, et al. Les mésothéliomes environnementaux en Corse du nord-est. Rev Mal Respir 1993b;10:339-45.         

27. Magnani C, Dalmasso P, Biggeri A, Ivaldi C, Mirabelli D. Increased risk of malignant mesothelioma of the pleura after residential or domestic exposure to asbestos: a case-control study in Casale Monferrato, Italy. Environ Health Perspect 2001;109(9):915-9. DOI: 10.1289/ ehp.01109915        

28. Pan XL, Day HW, Wang W, Beckett LA, Schenker MB. Residential proximity to naturally occurring asbestos and mesothelioma risk in California. Am J Respir Crit Care Med 2005;172:1019-25. DOI: 10.1164/rccm.2004121731OC        

29. Whitehouse AC, Black CB, Heppe MS, Ruckdeschel J, Levin SM. Environmental exposure to Libby Asbestos and mesotheliomas. Am J Ind Med 2008;51(11):877-80. DOI: 10.1002/ajim.20620        

30. Luo S, Liu X, Mu S, Tsai SP, Wen CP. Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data. Occup Environ Med 2003;60:35-41.         

31. Baris YI, Sahin AA, Ozesmi M, Kerse I, Ozen E, Kolacan B, et al. An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Krain/Urgüp in Anatolia. Thorax 1978;33:181-92.         

32. Baris YI, Saracci R, Simonato L, Skidmore JW, Artvinli M. Malignant mesothelioma and radiological chest abnormalities in two villages in Central Turkey. An epidemiological and environmental investigation. Lancet 1981;1(8227):984-7.         

33. Baris YI, Grandjean P. Prospective study of mesothelioma mortality in Turkish villages with exposure to fibrous zeolite. J Natl Cancer Inst 2006;98:414-7. DOI: 10.1093/ jnci/djj106        

34. Sébastien P, Awad L, Bignon J, Petit G, Barris YI. Ferruginous bodies in sputum as an indication of exposure to airborne mineral fibers in the mesothelioma villages of Cappadocia. Arch Environ Health 1984;39:18-23. DOI: 10.1080/00039896.1984.10545828        

35. Dumortier P, Coplü L, Broucke I, Emri S, Selcuk T, de Maertelaer V, et al. Erionite bodies and fibers in bronchoalveolar lavage fluid (BALF) of residents from Tukzoy, Cappadocia, Turkey. Occup Environ Med 2001;58:261-6.         

36. Goldberg P, Goldberg M, Marne MJ, Hirsch A, Tredaniel J. Incidence of pleural mesothelioma in New Caledonia: a 10-year survey (1978-1987). Arch Env Health 1991;46:306-9. DOI: 10.1080/00039896.1991.9934393        

37. Baumann F, Maurizot P, Mangeas M, Ambrosi JP, Douwes J, Robineau B. Pleural mesothelioma in New Caledonia: associations with environmental risk factors. Environ Health Perspect 2011;119(5):695-700. DOI: 10.1289/ ehp.1002862.         

38. Bayram M, Dongel I, Bakan ND, Yalçin H, Cevit R, Dumortier P, Nemery B. High risk of malignant mesothelioma and pleural plaques in subjects born close to ophiolites. Chest 2013;143(1):164-71. DOI: 10.1378/ chest.11-2727        

39. Conti S, Minelli G, Manno V, Iavarone I, Comba P, Scondotto S, Cernigliaro A. Health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla: mortality and hospitalization from current data. Ann Ist Super Sanità 2014. This issue.         

40. Safe Work Australia. Mesothelioma in Australia Incidence 1982 to 2008 Deaths 1997 to 2007. Available from:        

41. Lanphear BP1, Buncher CR. Latent period for malignant mesothelioma of occupational origin. J Occup Med 1992;34(7):718-21.         

42. Bianchi C1, Giarelli L, Grandi G, Brollo A, Ramani L, Zuch C. Latency periods in asbestos-related mesothelioma of the pleura. Eur J Cancer Prev 1997;6(2):162-6.         

43. Marinaccio A, Binazzi A, Cauzillo Gb, Cavone D, De Zotti R, Ferrante P, Gennaro V, Gorini G, Menegozzo M, Mensi C, Merler E, Mirabelli D, Montanaro F, Marina M, Pannelli F, Romanelli A, Scarselli A, Tumino R. Italian Mesothelioma Register (ReNaM) Working Group. Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register. Eur J Cancer 2007;43(18):2722-8.         

44. Consonni D. Something is missing: what's wrong with using age at diagnosis/death or latency among cases. Epidemiol Prev 2013;37(1):85-8.         



Submitted on invitation.
Accepted on 18 April 2014.



Address for correspondence:
Caterina Bruno, Dipartimento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.

Istituto Superiore di Sanità Roma - Rome - Italy