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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. 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. 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). 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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ORIGINAL ARTICLE
Malignant mesothelioma due to non-occupational
asbestos exposure from the Italian national surveillance
system (ReNaM): epidemiology and public health issues
Alessandro Marinaccio,
1
Alessandra Binazzi,
1
Michela Bonafede,
1
Marisa Corati,
1
Davide Di Marzio,
1
Alberto Scarselli,
1
Marina Verardo,
2
Dario Mirabelli,
3
Valerio Gennaro,
4
Carolina Mensi,
5
Gert Schallemberg,
6
Enzo Merler,
7
Corrado Negro,
8
Antonio Romanelli,
9
Elisabetta Chellini,
10
Stefano Silvestri,
10
Mario Cocchioni,
11
Cristiana Pascucci,
11
Fabrizio Stracci,
12
Valeria Ascoli,
13
Luana Trafcante,
14
Italo Angelillo,
15
Marina Musti,
16
Domenica Cavone,
16
Gabriella Cauzillo,
17
Federico Tallarigo,
18
Rosario Tumino,
19
Massimo Melis,
20
ReNaM Working Group
For numbered afliations see
end of article.
Correspondence to
Dr Alessandro Marinaccio,
Italian WorkersCompensation
Authority (INAIL), Department
of Occupational and
Environmental Medicine,
Epidemiology and Hygiene,
Unit of Occupational and
Environmental Epidemiology,
Italian Mesothelioma Register,
Via Stefano Gradi 55,
Rome 00143, Italy;
a.marinaccio@inail.it
Received 29 April 2014
Revised 31 October 2014
Accepted 25 November 2014
To cite: Marinaccio A,
Binazzi A, Bonafede M,
et al.Occup Environ Med
Published Online First:
[please include Day Month
Year] doi:10.1136/oemed-
2014-102297
ABSTRACT
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
Mesoteliomiin 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 denes 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 bres 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 signicantly 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.
INTRODUCTION
Asbestos is a natural brous mineral of hydrate sili-
cates, generally classied in amphiboles (actinolite,
amosite, anthophyllite, crocidolite and tremolite) and
serpentine (chrysotile), showing different chemical
and physical properties. It has unusual characteristics
of plasticity and properties of high tensile strength,
and thermal and chemical resistance.
Recently, the International Agency for Research
on Cancer conrmed all forms of asbestos as car-
cinogenic for humans (group 1). There is sufcient
evidence that asbestos causes mesothelioma and
cancer of the lung, larynx and ovary. Positive asso-
ciations have also been observed between exposure
to all forms of asbestos cancer (malignant meso-
thelioma) and cancer of the pharynx, stomach,
What this paper adds
Malignant mesothelioma is a rare tumour
which can also occur after low levels of
asbestos exposure.
Epidemiological analytical studies have
repeatedly reported a signicant risk of
mesothelioma for people exposed to asbestos
in non-occupational settings.
We documented that 10.2% of mesothelioma
cases are due to non-occupational exposure to
asbestos as suggested by the ndings of a
large epidemiological national surveillance
system (15 845 cases and 12 065 individuals
interviewed).
The most signicant source of risk is
cohabitation with an occupationally exposed
patient or residence near an asbestos cement
plant; asbestos exposure during leisure
activities is difcult to identify and probably
underestimated.
It is necessary to dene policies and strategies
for increasing prevention tools and for dealing
with compensation rights for malignant
mesothelioma cases induced by
non-occupational exposure to asbestos.
Marinaccio A, et al.Occup Environ Med 2015;0:18. doi:10.1136/oemed-2014-102297 1
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colon and rectum.
1
Malignant mesothelioma (MM) is a tumour
arising from the serous membranes of the pleura and, less fre-
quently, of the peritoneal and pericardial cavities and from the
testis tunica vaginalis. Prognosis is poor and average survival is
912 months from diagnosis for pleural and even lower for
peritoneal forms.
Many western countries are currently going through an MM
epidemic, considering the extensive use of asbestos between the
1950s and the 1980s in several industrial applications and the
long latency period (around 40 years) from the beginning of
exposure. Moreover, asbestos is still extensively used in many
countries in Asia, South America, Africa and in the former
Soviet Union; at present, 125 million people have been esti-
mated to be exposed to asbestos worldwide.
2
In the countries that have banned asbestos, the majority of
asbestos-related diseases are caused by occupational exposure
that occurred in the past. Nevertheless, assessment of the spread
and of the health effects of non-occupational asbestos exposure
continues to be of great public interest because it is related to
peculiar exposure circumstances like living with asbestos
workers or close to asbestos mines or manufacturing plants, or
naturally occurring asbestos bres, or in asbestos-insulated build-
ings.
3
In the past four decades, excesses of incidence of meso-
thelioma and cancer of the lung have been reported as a
consequence of the natural presence of asbestos (or asbestos-
like) material in rural areas in Turkey,
4
Greece,
5
Corsica in
France,
6
Biancavilla (Sicily) in Italy,
7
New Caledonia,
8
China
9
and California in the USA.
10
The increased risk of cancer for
population groups resident in the vicinity of raw asbestos pro-
duction sites (mines or mills), as well as for people living close
to industrial manufacturing plants producing material contain-
ing asbestos, has been demonstrated.
1113
In Italy, 3 748 550 tons of raw asbestos were produced up to
the 1992 ban, with a peak between 1976 and 1980 at more than
160 000 tons/year; asbestos consumption decreased in Italy
since 1980s only (around ten years later with respect to other
industrialised countries).
14
As environmental exposure related to
residence near asbestos-cement plants has been repeatedly
reported for Casale Monferrato,
15
Bari,
16
Broni
17
and La
Spezia,
18
this usage pattern may have led to sustained non-
occupational exposures. The contribution of different patterns of
non-occupational exposures is most likely underestimated, due to
their much lower level, which, however, is not negligible and is
possibly sufcient to cause disease. A permanent surveillance
system of mesothelioma incidence in Italy has been run since
2002 by the National Register of Malignant Mesotheliomas
(ReNaM, Registro Nazionale dei Mesoteliomiin Italian) iden-
tifying cases and assessing asbestos exposure.
19
The purpose of the present study is to present data about
non-occupationally exposed MM case currently available in the
ReNaM archive. The gure is discussed with respect to compen-
sation and welfare system efciency for people exposed in the
past and to asbestos exposure prevention strategies for the
present.
METHODS
The epidemiological surveillance of mesothelioma incidence is
conducted in Italy by a specic register drawn up, by law, in
2002. ReNaM has a regional structure: a Regional Operating
Centre (COR) has gradually been established in all Italian
regions except the Molise region and an autonomous province
of Bolzano, covering almost the whole country (98.5% of the
Italian population). Each COR works applying the national stan-
dardised methods described in the specic guidelines.
20
They
actively search for MM cases by obtaining information from
healthcare institutions that diagnose and treat cases (especially
pathology units and lung care and chest surgery wards).
Diagnostic coding criteria have been established by means of a
grid according to three classes of decreasing level of certainty:
certain, probable and possible MM. Occupational history, life-
style and residential history are obtained using a standardised
questionnaire, administered by a trained interviewer, to the
patient or to the next of kin after informed consent expressed
by the cases or their relatives at the beginning of the interview.
CORs may consult local public health and safety agencies to
gain supplementary information on occupational and/or residen-
tial exposure. In each COR, an industrial hygienist, or a panel
of industrial hygienists, classies and codes the exposure by
examining the information collected. Moreover, an agreement
between the Italian WorkersCompensation Authority (INAIL)
and the Italian Social Security Institute (INPS) makes it possible
to retrieve pension contributions from personal data. Therefore,
in many cases, INAIL may provide CORs with information
about occupational histories of mesothelioma cases, either as a
conrmation of information obtained directly from the patient,
or as a major information source when the interview is not
available.
Occupational exposure classication can be assigned as den-
ite, probable or possible. Denite occupational exposure refers
to people whose work has involved the use of asbestos or mate-
rials containing asbestos. Probable occupational exposure refers
to people who have worked in a rm where asbestos was cer-
tainly used, but whose exposure cannot be documented, and
possible occupational exposure to people who have worked in
rms in an economic sector where asbestos has been used.
Further, specic codes are assigned to familial exposure (when
patients have lived with a person occupationally exposed to
asbestos), environmental (residence near a source of asbestos
pollution without work-related exposure) and leisure activities.
Modalities of exposure are assigned with an exclusive and hier-
archical methodology: cases dened as familial exposurehad
no occupational exposure, whereas cases having environmental
exposurehad neither familial nor occupational exposure.
Finally, cases classied as due to leisure activities exposurehad
no other relevant circumstances of exposure. The data collected
by each COR are then periodically sent to ReNaM and stored in
a centralised database. All procedures and systems of classica-
tions and codes are more extensively described in the aforemen-
tioned guidelines.
To date, ReNaM has collected cases with a diagnosis of MM
in the period 19932008; the collection and analyses of data
for the period of incidence 20092012 are ongoing. Italian
regions did not contribute homogenously during this period:
Piedmont, Veneto, Tuscany and Apulia produced incidence
regional data starting from 1993, Basilicata from 1995, Liguria,
Emilia-Romagna and Marche from 1996, Sicily from 1998,
Lombardy, Friuli-Venezia Giulia and Valle DAosta from 2000,
Campania from 2001 and Umbria from 2006. The data from
Calabria and Sardinia cannot be considered complete with
regard to the incidence of the disease. Finally, Trentino
Alto-Adige only collected data for the province of Trento (half
of the resident people and territorial extension of the Region).
The province of Bolzano and Molise region have still not con-
tributed to the network. Standardised incidence rates have been
calculated with the direct method for the territorial coverage of
incidence data and with population at the national census at
2001 used as the denominator and for age standardisation. The
exposure data analyses pertain to the whole ReNaM database
2 Marinaccio A, et al.Occup Environ Med 2015;0:18. doi:10.1136/oemed-2014-102297
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including data from regions with incomplete incidence gures.
All statistical analyses were carried out with the SPSS software
(V.21.0).
RESULTS
In the period between 1993 and 2008, a list of 15 845 cases of
MM were identied. The pleural site was reported in 93%
(14 736 cases), while peritoneal cases accounted for 6.4% of the
total number (1017 cases); pericardial and testicular cases
accounted for 0.3% (41 and 51 cases, respectively). The male/
female ratio was 2.6 among pleural cases, and 1.4 and 1.9 among
peritoneal and pericardial ones, respectively. The mean age at
diagnosis was 68.3 years (SD±10.6) in men and 69.8 (SD
±11.6) in women. People aged less than 45 years were rare,
accounting for 2.4% of all recorded MM cases. The standardised
incidence rate for pleural mesothelioma (certain, probable and
possible) in 2008 was 3.84 cases per 100 000 inhabitants for
men and 1.45 for women; 0.26 and 0.12, respectively, for the
peritoneal site and less than 1 case per million inhabitants for
pericardial and tunica vaginalis testis forms. The modalities of
exposure to asbestos bres were investigated for 12 065 (76.1%)
of the 15 845 cases collected. This percentage was not constant
geographically and showed great variability (higher than 90% in
Lombardy, Tuscany, Apulia, Umbria and the province of Trento;
lower than 50% in Sicily, Campania and Calabria). For 8367
cases (69.3% of the 12 065 cases for which the exposure den-
ition is available), the modalities of asbestos exposure were classi-
ed as occupational (denite, probable, possible); for 2466 cases
(20.4%), we found no asbestos exposure.
19
The list of cases dened as non-occupationally exposed
includes 1232 individuals. We found 530 (4.4%) MM cases
with familial exposure (they have lived with a person who was
occupationally exposed), 514 MM cases (4.3%) with environ-
mental exposure to asbestos (they lived near sources of asbestos
pollution and have not been occupationally exposed) and 188
(1.6%) with exposure due to hobby-related or leisure activities.
The proportion of MM cases due to non-occupational asbestos
exposure (familial, environmental or related to leisure activities)
was 10.2% at the national level with signicant territorial vari-
ability and the highest values in Piedmont (24.4%), Trento
autonomous province (15.6%), Puglia (14.4%) and Veneto
(13.5%). The female/male ratio was 2.3:1 for the whole popula-
tion with non-occupational exposure, but it reached the value of
5.9:1 focusing on MM cases with exclusively familial modalities
of exposure.
Table 1 shows the demographic, diagnostic and personal
history characteristics of the 1232 MM cases with non-
occupational exposure to asbestos. As an individual may have
had multiple exposure, 1427 causally relevant exposures were
registered for the 1232 cases included in the analysis. Table 2
describes these 1427 modalities of exposures in detail. For the
530 cases classied as having familial aetiology, we considered
only familial exposure circumstances, ignoring environmental
exposures, if any. This choice is consistent with recent simula-
tions of low-level exposed workers that show asbestos levels com-
mensurate with background concentrations in those exposed
domestically.
21
In table 3, occupationally and non-occupationally exposed MM
cases are compared with respect to selected epidemiological para-
meters. A statistically signicant difference in mean age at diagno-
sis was found between occupationally and non-occupationally
exposed cases (68.1 vs 67.2 years, p<0.01) and in non-
occupationally exposed cases by gender (66 vs 68 years for men
and women, respectively, p<0.05). The values range from
69.3 years (SD±11.01) for leisure exposed to 67.5 (SD±11.8) for
familial and 66.1 (SD±13.6) for environmental, with a statistically
signicant difference by gender in familial cases (p<0.0001):
68 (SD±11.5) in women versus 63 (SD±12.6) years in men.
Mean age at rst exposure was lower among those with non-
occupational exposure compared to the occupational cases (18.5
vs 22.5 years, p<0.0001). Latency time, dened as the time elap-
sing between the beginning of asbestos exposure and MM diagno-
sis, shows higher median values overall for non-occupational
exposure than occupational exposure (46 years, SD±12): 51 years
(SD±14) in familial exposures (although lower in women,
49.5 years, than in men, 55 years) and 49 years (SD±16) in envir-
onmental exposures (again lower in women, 47 years, than in
men, 53 years). Conversely, in leisure activities, the median latency
times is 43.5 years, signicantly different by gender (48 vs
37 years, respectively, for men and women, p<0.001).
Figure 1 shows the geographical distribution of MM cases
due to familial, environmental and leisure activities collected by
Table 1 MM cases (N, %) collected by the National
Mesothelioma Register (ReNaM) due to familial, environmental and
leisure activity exposure by gender, age, anatomical site, period of
diagnosis, level of diagnostic certainty, morphology and modalities
of interview (Italy, 19932008)
Men Women
N Per cent N Per cent
Exposure modalities
Familial 77 20.6 453 52.8
Environmental 217 58.0 297 34.6
Leisure activities 80 21.4 108 12.6
Pleural 348 93.0 801 93.4
Anatomical sites
Peritoneum 23 6.1 56 6.5
Pericardium 0 0.0 1 0.1
Tunica vaginalis of the testis 3 0.8 ––
Age classes
044 24 6.4 36 4.2
4564 147 39.3 276 32.2
6574 93 24.9 274 31.9
+75 110 29.4 272 31.7
19931996 42 11.2 62 7.2
19972000 86 23.0 172 20.0
Period of diagnosis
20012004 125 33.4 327 38.1
20052008 121 32.4 297 34.6
Diagnostic certainty
MM certain 318 85.0 700 81.6
MM probable or possible 56 15.0 158 18.4
Morphology
Epithelioid 226 60.4 523 61.0
Fibrous 40 10.7 50 5.8
Biphasic 46 12.3 93 10.8
MM NOS 36 9.6 107 12.5
Not available 26 7.0 85 9.9
Exposure detection
Direct interview 200 53.5 392 45.7
Indirect interview 173 46.3 464 54.1
No interview, other information source 1 0.3 2 0.2
Overall 374 100.0 858 100.0
MM, malignant mesothelioma; NOS, not otherwise specified.
Marinaccio A, et al.Occup Environ Med 2015;0:18. doi:10.1136/oemed-2014-102297 3
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ReNaM in the Italian territory. The map makes it possible to
identify the areas of asbestos pollution contamination due to the
presence of asbestos-cement industry plants (Casale Monferrato,
Broni and Bari), areas of shipbuilding and repair (Monfalcone,
Trieste, La Spezia, Genova, Castellamare di Stabia, Livorno and
Taranto) and areas of environmental exposure in Biancavilla
Table 2 Modalities of exposure of malignant mesothelioma (MM) cases (N, %) collected by the National Mesothelioma Register (ReNaM)
disentangled by familial, environmental or leisure activity exposure categories and gender (Italy, 19932008)
Men Women
Number of exposures* Per cent Number of exposures* Per cent
Familial: cohabitation with (530 MM cases)
Parents 74 74.0 138 23.9
Husband/wife 3 3.0 354 61.4
Son/daughter 5 5.0 27 4.7
Other cohabitants 18 18.0 58 10.1
Overall 100 100 577 100
Environmental: residence near (514 MM cases)
Asbestos cement plant 103 43.6 144 44.6
Railways 18 7.6 22 6.8
Rail stock building, repair and demolition plant 10 4.2 7 2.2
Docks 8 3.4 6 1.9
Shipbuilding and repair 8 3.4 7 2.2
Steel industry plants 2 0.8 12 3.7
Chemical or petrochemical plants 7 3.0 8 2.5
Mines or mills 7 3.0 9 2.8
Others 73 30.9 108 33.4
Overall 236 100 323 100
Use of asbestos materials containing asbestos29 34.5 92 80.7
Home masonry 25 29.8 3 2.6
Thermal insulation at home 9 10.7 2 1.8
Leisure activities (188 MM cases)
Plumbing or electric repair at home 2 2.4 2 1.8
Car repair 4 4.8
Other activities 15 17.9 15 13.2
Overall 84 100 114 100
*The number of exposures exceeds the number of mesothelioma cases due to the possibility of multiple exposures for a single case.
Including exposures due to the presence of asbestos in objects not used in a working context (eg, ironing boards, rural tool sheds).
Table 3 Mean age at diagnosis.
Number Years (SD) p Value
Mean age at diagnosis
Occupational exposure 8367 68.1 (±10) Ref
Non-occupational exposure 1232 67.2 (±12.3) <0.01
Familial 530 67.5 (±11.8) 0.161
Environmental 514 66.1 (±13.6) <0.001
Leisure activities 188 69.3 (±11.01) 0.108
Mean age at first exposure
Occupational exposure 8367 22.5 (±8.3) Ref
Non-occupational exposure 1232 18.5 (±15.6) <0.001
Familial 530 17 (±14.3) <0.001
Environmental 514 17 (±16.2) <0.001
Leisure activities 188 27 (±14.5) <0.001
Median latency
Occupational exposure 8367 46 (±12) Ref
Non-occupational exposure 1232 49 (±15) <0.001
Familial 530 51 (±14) <0.001
Environmental 514 49.5 (±16) <0.001
Leisure activities 188 43 (±14.1) <0.01
Mean age at first exposure and median latency period of malignant mesothelioma cases collected by the National Mesothelioma Register (ReNaM) by modalities of exposure (Italy,
19932008).
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(Sicily) due to the local presence of uoroedenite (an amphibole
asbestiform mineral), a contaminating material massively used
for construction and road paving in the area.
DISCUSSION
MM is a major public health issue considering the increasing
incidence in many countries; the still complex and difcult
Figure 1 Geographical distribution of malignant mesothelioma (MM) cases due to environmental, familial, leisure activities collected by the
National Mesothelioma Register (ReNaM) by municipalities of residence at diagnosis. Italy, 19932008. Labels and circle graphs are reported for
municipalities with at least six MM cases with environmental (E, in green) or familial (F, in red) or leisure activities-related (L, in blue) exposure to
asbestos. Selected municipalities are Casale Monferrato (92 MM cases due to environmental exposure in the period, 68 due to familial exposure,
4 leisure activities-related exposure), Torino (37, 25, 7), Collegno (7, 4, 0) in Piedmont; Genova (6, 32, 16), La Spezia (4, 9, 2) in Liguria; Milano
(18, 3, 18), Broni (26, 7, 0), Stradella (9, 2, 4) in Lombardy; Padova (12, 7, 2), Venezia (4, 14, 0) in Veneto; Trieste (0, 9, 0), Monfalcone (1, 7,
0) in Friuli-Venezia Giulia; Reggio Emilia (1, 9, 1), Bologna (4, 2, 1), Parma (4, 4, 1), Ravenna (2, 5, 1) in Emilia-Romagna; Livorno (1, 5, 0) in
Tuscany; Roma (4, 4, 1) in Lazio; Bari (42, 3, 1), Taranto (13, 5, 1) in Apulia; Biancavilla (7, 0, 0) in Sicily.
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diagnosis, staging and treatment; the poor prognosis, which is
not improving, and the implications for welfare and insurance
systems due to the occupational origin for many patients. The
close relationship with asbestos exposure has been demonstrated
by a large amount of data, although the recognition of patho-
genetic mechanisms is still incomplete. All forms of asbestos
cause mesothelioma, prevalently of the pleura but also of the
serous membranes of the peritoneum, lung, ovary and larynx
cancers. A positive association has been reported for cancers of
the colon and rectum, stomach and pharynx.
1
Asbestos has been
banned in many industrialised countries but is still mined and
used in a large part of the world.
22
As a legacy of the massive
use of asbestos, Italy is today one of the countries most involved
in the monitoring, surveillance and control of asbestos-related
diseases.
23
Similar experiences to the Italian mesothelioma inci-
dence surveillance system, with regard to methods and exten-
sion, are scarce and, to the best of our knowledge, currently
ongoing only in France
24
and Australia.
25
Critical limitations of the ReNaM data set have to be discussed
preliminarily. Some regions of the Italian network were collecting
incidence cases even before the beginning of the national register
in 1993, but others started later or are not yet participating. Any
evaluation of the trend of MM incidence is therefore strongly
limited. The ability/effectiveness to identify the modalities of
exposure is not fully consistent between regions and the percent-
age of patients interviewed varies between 45% and 95%
depending on the available resources and knowledge. CORs
activities began not at the same year, as started in Methods, and
this could inuence incidence and asbestos exposure ndings.
Although the coding and classifying systems (for diagnosis and
exposure) such as the questionnaire for the anamnestic survey
and the operative procedure are nationally established, neverthe-
less the possible lack of homogeneity among CORs in the prac-
tice is a crucial and real issue. The identication and assessment
of the different asbestos exposure modalities actually represents a
key factor of the ReNaM register that can help in dening the
strategies to prevent the health risks/effects for the population
and to guarantee a proper welfare protection. At present in Italy,
the issue of insurance and welfare protection for mesothelioma
cases due to non-occupational exposure to asbestos is under
debate. Different modalities of non-occupational exposure to
asbestos pose different concerns with respect to the welfare pro-
tection framework.
Environmental exposure from naturally occurring asbestos
contamination of the soil has been documented in Turkey,
where mesothelioma epidemics due to the presence of tremolite,
chrysotile and erionite, belonging to the zeolite family, have
been proved.
26
In Greece, a high frequency of pleural calcica-
tion was found in patients living in places where no industrial
use of asbestos was documented in the past, but tremolite bres
have been found in the soil used to make whitewash that was
commonly applied to homes in the affected areas.
27
Natural
contamination of the soil with tremolite bres has also been
detected in Cyprus
28
and Corsica,
6
as evidenced by occurrences
of asbestos-related diseases without any asbestos use for indus-
trial applications. Similarly, cases of pleural mesothelioma in
New Caledonia have been signalled due to the use of a white-
wash material primarily containing tremolite bres,
29
and in
Chinese rural areas they appear to be related to the presence of
crocidolite outcrops.
9
Cases of mesothelioma have been found
in the town of Libby (Montana, USA), close to which there
operated the worlds largest vermiculite mine, vermiculite being
extensively used in the surrounding residential zone,
11
and in
the township of Wittenoom (Western Australia), where a
crocidolite mine was active from 1943 to 1966 with extensive
use of the tailings to pave roads, footpaths and school play-
grounds.
30
In Italy, three MM cases due to tremolite pollution
in a rural area of Basilicata have been signalled,
31
while in the
area of Biancavilla Etnea (Sicily) an excess of mortality due to
pleural tumours has been observed and subsequent analyses
have conrmed the causal role of a mine in the neighbourhood
extracting a uoroedenite-contaminated material massively used
for construction and road paving.
7
The risk of mesothelioma
associated with local industrial sources was clearly demonstrated
for the neighbouring populations.
32 33
The spatial variation in
the mesothelioma risk in an area highly polluted by the
asbestos-cement plant in Casale Monferrato has been discussed,
adjusting for occupational and domestic exposures, highlighting
the fact that the effect on the general population of pollution
from industrial sources decreases with increasing distance from
the factory.
34
Mesothelioma cases due to cohabitation with
exposed people have been attributed to soiled work clothes
brought home. An Italian cohort study of wives of Casale
Monferrato asbestos-cement factory workers showed a large
excess of pleural mesothelioma (standardised mortality ratio,
SMR=18.00, 21 observed vs 1.2 expected).
35
Evidence is also
accumulating about passive asbestos exposure in asbestos-
containing buildings, such as public ofces or schools, where
the people involved have no awareness of direct physical contact
with asbestos-containing material.
36
Estimates of the proportion of individuals non-occupationally
exposed to asbestos, as well as of the relative contribution of non-
occupational and occupational exposures to incidence, are rarely
available,
37
although analyses of the incident trend for MM cases
for different categories of exposure are reported.
38
Our study pro-
vides a reliable estimation of 10% (1232 cases) for MM cases due
to non-occupational asbestos exposure based on more than
15 845 detected cases, of which 12 065 were individually inter-
viewed. This estimate is strongly related to specic Italian patterns
of exposure. The distribution of modalities of exposure shows that
familial exposure is the most frequent in non-occupationally
exposed cases, although it has to be considered that asbestos
exposure during leisure activities is difcult to identify and prob-
ably underestimated. Residence near asbestos cement plants is
largely predominant in the environmentally exposed patients.
However, the analytical description of living conditions (historical
residence) and habits (leisure time and hobby activities) involved
in the risk of asbestos exposure remains of great value for primary
prevention and public health policies.
The design of our study (an incidence surveillance system),
the possible presence of competitive causes of death and the
limited period of observation prevent statistical inferences on
the association between exposure and time to event (age or
latency).
39 40
Non-occupational exposure exhibits some dis-
tinctive features that deserve special attention. One is that the
individuals involved were especially likely to be unaware of
their exposure or of the associated hazard, as in the case of
people living around industrial sources of asbestos pollution
and/or with asbestos workers. Another one is the considerably
younger age at the start of exposure, which provides the
opportunity for accruing a longer duration of exposure and
latency.
Accordingtoourndings, asbestos pollution outside the
workplaces signicantly contributes to the burden of asbestos-
related diseases. The evaluation of a framework for dealing
with compensation rights for MM cases induced by non-
occupational exposure to asbestos needs to be carefully under-
taken from the economic, ethical and insurance points of view.
6 Marinaccio A, et al.Occup Environ Med 2015;0:18. doi:10.1136/oemed-2014-102297
Environment
group.bmj.com on June 9, 2015 - Published by http://oem.bmj.com/Downloaded from
Finally, the identication of an environmental source of con-
tamination, by means of a specialised surveillance system for
MM incidence inclusive of individual exposure assessment,
remains an important tool for primary prevention of risks.
Author afliations
1
Italian WorkersCompensation Authority (INAIL), Department of Occupational and
Environmental Medicine, Epidemiology and Hygiene, Unit of Occupational and
Environmental Epidemiology, Italian Mesothelioma Register, Rome, Italy
2
Valle dAosta Health Local Unit, Regional Operating Centre of Valle dAosta (COR
Valle dAosta), Aosta, Italy
3
COR Piedmont, Unit of Cancer Prevention, University of Turin and CPO-Piemonte,
Torino, Italy
4
COR Liguria, UO Epidemiology, IRCCS Azienda Ospedaliera Universitaria San
Martino, National Cancer Research Institute (IST), Genova, Italy
5
COR Lombardy, Department of Preventive Medicine, Fondazione IRCCS CaGranda,
Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
6
COR Province of Trento, Provincial Unit of Health, Hygiene and Occupational
Medicine, Trento, Italy
7
COR Veneto, Occupational Health Unit, Department of Prevention, Padua, Italy
8
Clinical Unit of Occupational Medicine, COR Friuli-Venezia Giulia, University of
TriesteTrieste General Hospitals, Trieste, Italy
9
COR Emilia-Romagna, Health Local Unit, Public Health Department, Reggio Emilia,
Italy
10
Unit of Environmental and Occupational Epidemiology, COR Tuscany, Cancer
Prevention and Research Institute, Florence, Italy
11
Environmental and Health Sciences Department, COR Marche, University of
Camerino, Hygiene, Camerino, Italy
12
Department of Hygiene and Public Health, COR Umbria, University of Perugia,
Perugia, Italy
13
Department of Experimental Medicine, COR Lazio, University La Sapienza, Rome,
Italy
14
COR Abruzzo, Health Local Unit, Occupational Medicine Unit, Pescara, Italy
15
Department of Experimental Medicine, COR Campania, Second University of
Naples, Naples, Italy
16
Department of Internal Medicine and Public Medicine, Section of Occupational
Medicine ‘‘B.Ramazzini’’, COR Puglia, University of Bari, Bari, Italy
17
COR Basilicata, Epidemiologic Regional Centre, Potenza, Italy
18
COR Calabria, Public Health Unit, Crotone, Italy
19
Ragusa Cancer Register Unit, COR Sicily, CivileM.P. ArezzoHospital, Ragusa,
Italy
20
COR Sardegna, Regional Epidemiological Centre, Cagliari, Italy
Acknowledgements The Italian National Mesothelioma Register (ReNaM) is a
collaborative network of institutions. The authors thank all COR persons involved in
identication and exposure assessment and Massimo Nesti for his precious work in
promoting and improving ReNaM.
Collaborators ReNaM Working Group members are: Detragiache E (COR Valle
dAosta); Merletti F, Gangemi M, Stura A, Brentisci C, Cammarieri Diglio G,
Macerata V, Gilardetti M (COR Piemonte); Benfatto L, Bianchelli M, Mazzucco G
(COR Liguria); Consonni D, Pesatori AC, Riboldi L (COR Lombardia); Bressan V,
Gioffrè F, Ballarin MN (COR Veneto); Chermaz C, De Michieli P (COR Friuli-Venezia
Giulia); Mangone L, Storchi C, Sala O (COR Emilia-Romagna); Badiali AM, Cacciarini
V, Giovannetti L, Martini A (COR Toscana); Pascucci C, Calisti R (COR Marche);
La Rosa F, DAloD, Petrucci MS (COR Umbria); Davoli M, Forastiere F, Cavariani F,
Romeo E, Ancona L (COR Lazio); Di Giammarco A (COR Abruzzo); Menegozzo S,
Canfora ML, Santoro M, Viscardi F, Brangi A, Cozza V (COR Campania); Baldassarre
A (COR Puglia); Lio SG (COR Calabria);, Nicita C, Dardanoni G, Scondotto S
(COR Sicilia); Nieddu V, Pergola M, Stecchi S (COR Sardegna).
Contributors AM designed the study, performed statistical analyses, interpreted
the data and drafted the manuscript. AB, MB, MCor, DDM and AS participated in
interpreting the data and in revising the manuscript. MV, DM, VG, CM, GS, EM,
CN, AR, EC, SS, MCoc, FS, VA, LT, IA, MMu, DC, GC, FT, RT, MMe and CP
collected data, dened asbestos exposure and participated in revising the
manuscript.
Funding This research was supported and funded by the Italian Ministry of Health,
Diseases Control Center (CCM), project n. 24/12 and by Italian Workers
Compensation Authority (INAIL), triennial research plan 20132015 ratied by the
INAIL scientic committee, programme P1, research line L1. The units of
epidemiology or occupational health hosting the Regional Operating Centres belong
to the National Health Service and are nanced by their health authorities.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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issues
(ReNaM): epidemiology and public health
the Italian national surveillance system
non-occupational asbestos exposure from
Malignant mesothelioma due to
Massimo Melis
Cavone, Gabriella Cauzillo, Federico Tallarigo, Rosario Tumino and
Ascoli, Luana Trafficante, Italo Angelillo, Marina Musti, Domenica
Silvestri, Mario Cocchioni, Cristiana Pascucci, Fabrizio Stracci, Valeria
Merler, Corrado Negro, Antonio Romanelli, Elisabetta Chellini, Stefano
Mirabelli, Valerio Gennaro, Carolina Mensi, Gert Schallemberg, Enzo
Corfiati, Davide Di Marzio, Alberto Scarselli, Marina Verardo, Dario
Alessandro Marinaccio, Alessandra Binazzi, Michela Bonafede, Marisa
published online June 4, 2015Occup Environ Med
http://oem.bmj.com/content/early/2015/06/04/oemed-2014-102297
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... Statistics are periodically published describing the proportion of cases with recognized occupational exposures and their distribution by industry and occupation [4]. Interestingly, it was found that about 10% of all Italian cases had no recognized exposure at work but had been exposed to asbestos in non-occupational settings [5]. ...
... Occupational and non-occupational circumstances that could have entailed exposure to asbestos were investigated using the standardized ReNaM questionnaire, administered by trained interviewers to all study subjects. A next of kin was interviewed in case of participants' death or when their conditions prevented direct interviews [5]. Lifetime occupational histories were collected for cases and controls, supplemented by job-specific modules allowing the description of the working environment, the tasks carried out by the interviewees or in their presence, the general ventilation and local exhaust systems. ...
... Unlagged and lagged (10-, 20-and 30-year lag) indices were calculated. Cases and controls also underwent the ReNaM standard assessment of the exposure source and probability [5]. Local experts, usually industrial hygienists or occupational health physicians with specific knowledge of the local past uses and natural occurrence of asbestos, performed such assessment. ...
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Background The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases’ exposures but cannot provide relative risk estimates. Objectives i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure–response relationship. Methods A population-based mesothelioma case–control study was conducted in 2012–2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI). Results Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16–1.42). Conclusions Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure–response relationship.
... Ndlovu [85] found that most South Africans with community-derived mesothelioma had not received compensation despite the existence of numerous asbestos trust funds. Marinaccio et al. [86] reported concern about Italian insurance and welfare protection for those with community exposure caused mesothelioma, noting that different pathways of non-occupational exposure posed different issues with respect to acceptability under the welfare protection frame-work. Gordon and Leigh [87], citing ARD risks to non-professionals exposed to asbestos cement products in home renovation or other do-it-yourself activities, maintained that manufacturers of asbestos-containing products have a continuing duty of care to inform users about asbestos risks. ...
... Registries have made many contributions to our knowledge of ARD in communities. The Italian National Register of Malignant Mesothelioma (ReNaM) has recorded mesotheliomas and collected asbestos exposure information from 1993 to the present for most of Italy [44,86]. A national study using ReNaM was able to identify distinct geographic clusters in communities where asbestos-cement plants had operated (Broni discussed above, Casale Monferrato, and Bari), and sites of shipbuilding and repair (Monfalcone, Trieste, La Spezia, Genova, Castellamare di Stabia, Livorno, and Taranto). ...
... A national study using ReNaM was able to identify distinct geographic clusters in communities where asbestos-cement plants had operated (Broni discussed above, Casale Monferrato, and Bari), and sites of shipbuilding and repair (Monfalcone, Trieste, La Spezia, Genova, Castellamare di Stabia, Livorno, and Taranto). A cluster was also identified in Biancavilla, Sicily, where naturally occurring asbestiform fluoro-edenite was used in construction and road paving [86]. Even in prior sites of asbestos-cement plants, where the industrial use of asbestos had been broadly similar, the relative proportions of mesotheliomas attributed to all nonoccupational exposures and to para-occupational, residential, and leisure-related environmental pathways, respectively, varied from town to town. ...
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Asbestos-related diseases (ARDs)—mesothelioma, lung cancer, and asbestosis—are well known as occupational diseases. As industrial asbestos use is eliminated, ARDs within the general community from para-occupational, environmental, and natural exposures are more prominent. ARD clusters have been studied in communities including Broni, Italy; Libby, Montana; Wittenoom, Western Australia; Karain, Turkey; Ambler, Pennsylvania; and elsewhere. Community ARDs pose specific public health issues and challenges. Community exposure results in higher proportions of mesothelioma in women and a younger age distribution than occupational exposures. Exposure amount, age at exposure, fiber type, and genetic predisposition influence ARD expression; vulnerable groups include those with social and behavioral risk, exposure to extreme events, and genetic predispositions. To address community exposure, regulations should address all carcinogenic elongated mineral fibers. Banning asbestos mining, use, and importation will not reduce risks from asbestos already in place. Residents of high-risk communities are characteristically exposed through several pathways differing among communities. Administrative responsibility for controlling environmental exposures is more diffuse than for workplaces, complicated by diverse community attitudes to risk and prevention and legal complexity. The National Mesothelioma Registries help track the identification of communities at risk. High-risk communities need enhanced services for screening, diagnosis, treatment, and social and psychological support, including for retired asbestos workers. Legal settlements could help fund community programs. A focus on prevention, public health programs, particularization to specific community needs, and participation is recommended.
... Pleural MM represent about 80% of all MM cases. MM is highly lethal and characterised by a long period of latency (about 40 years and over) [1]. More than 80% of MM cases are attributable to asbestos exposure. ...
... Estimating the burden of MM cases due to non-occupational exposure is particularly difficult, though the risk of pleural mesothelioma caused by the residence near asbestos fibres sources (quarries, asbestos-cement plants) is known [1,6]. Some estimates show that about 20% of MM cases at global level could be caused by non-occupational exposure to asbestos [6]. ...
... For 20% of cases, asbestos exposure was unlikely or unknown [9]. On the basis of exposure ways reported in ReNaM database, clusters of MM cases due to environmental exposure were mainly related to the presence of asbestos-cement plants, shipbuilding and repair activities and soil contamination [1]. Regarding the last asbestos exposure source, local investigations reported an exceeding risk of MM in some Italian areas with naturally asbestos fibres presence [10,11]. ...
Article
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This study describes mortality from MM in Italy in people younger than 50 years (≤50 ys) and its geographical distribution, as a possible marker for environmental exposure to asbestos in children.
... The global burden of asbestos-related occupational diseases has been estimated at around 231,000 cases/year [3]. The major source of asbestos exposure is in work settings, but the health effects of environmental exposure are also recognized, with estimates of the proportion of total malignant mesothelioma cases ranging between 5 and 20% [4,5]. ...
... Clusters of mesothelioma cases among populations residing close to industrial contaminated sites (mostly with asbestos cement plants) were also reported recently [5,[27][28][29]. Furthermore, the more recent update of the national surveillance plan based on mortality data, highlighted clusters of deaths from mesothelioma in specific areas of the country and an increasing annual trend in the 2003-2014 period, particularly among the male population [18]. ...
Article
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Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010–2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10–25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.
... Regarding the type of exposure, in this paper we adopt the term "anthropogenic environmental exposure," referring to people who lived in an area with air-dispersed asbestos from the asbestos cement plant [30,31]. The term "occupational exposure" refers to people who worked in the asbestos cement industry [32]. ...
... In six cases, the environmental exposure was both residential and household. The relevance of non-occupational exposure in the determination of the asbestos fiber burden in lungs is in conformity with previous epidemiological studies [23,30,39,[43][44][45], as well as with previous electron microscope investigations [14,15]. This finding is in line with the concept that asbestos concentrations in lungs due to anthropogenic environmental exposure can be as high as those provoked by occupational exposure, as stated, as well, by the above cited papers. ...
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Increased mortality due to malignant mesothelioma has been demonstrated by several epidemiologic studies in the area around Broni (a small town in Lombardy, northern Italy), where a factory producing asbestos cement was active between 1932 and 1993. Until now, the inorganic fiber burden in lungs has not been investigated in this population. The aim of this study is to assess the lung fiber burden in 72 individuals with previous occupational and/or anthropogenic environmental exposure to asbestos during the activity of an important asbestos cement factory. Inorganic fiber lung burden was assessed in autoptic samples taken from individuals deceased from asbestos-related diseases using a scanning electron microscope equipped with an energy-dispersive spectrometer. Significant differences in the detected amount of asbestos were pointed out among the three types of exposure. In most lung samples taken from patients who died of mesothelioma, very little asbestos (or, in some cases, no fibers) was found. Such subjects showed a significantly lower median amount of asbestos as compared to asbestosis. Almost no chrysotile was detected in the examined samples. Overall, crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos, and anthophyllite asbestos. There were significant differences in the amount of crocidolite and amosite fibers according to the kind of exposure. Overall, these findings provide novel insights into the link between asbestos exposure and mesothelioma, as well as the different impacts of the various types of asbestos on human health in relation to their different biopersistences in the lung microenvironment.
... In the Italian mesothelioma national surveillance system, malignant mesothelioma due to non-occupational exposure represented 10% of overall cases. Of these, environmental and domestic exposures tended to be more prevalent in women [33] although at lower levels compared to those reported in workplaces. Similar findings were described in the municipality of Broni, Italy: of 147 MM cases registered between 2000 and 2011, only 38 were occupationally related, and of the non-occupational cases, domestic asbestos exposure prevailed in women while male exposure was primarily related to the environmental [34]. ...
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The aim of this study is to compare the mortality rates for typical asbestos-related diseases (ARD-T: mesothelioma, asbestosis, and pleural plaques) and for lung and ovarian cancer in Brazilian municipalities where asbestos mines and asbestos-cement plants had been operating (areas with high asbestos consumption, H-ASB) compared with in other municipalities. The death records for adults aged 30+ years were retrieved from multiple health information systems. In the 2000–2017 time period, age-standardized mortality rates (standard: Brazil 2010) and standardized rate ratios (SRR; H-ASB vs. others) were estimated. The SRRs for ARD-T were 2.56 for men (257 deaths in H-ASB municipalities) and 1.19 for women (136 deaths). For lung cancer, the SRRs were 1.33 for men (32,604 deaths) and 1.19 for women (20,735 deaths). The SRR for ovarian cancer was 1.34 (8446 deaths). Except for ARD-T and lung cancer in women, the SRRs were higher in municipalities that began using asbestos before 1970 than in municipalities that began utilizing asbestos from 1970 onwards. In conclusion, the mortality rates for ARD-T, and lung and ovarian cancer in municipalities with a history of asbestos mining and asbestos-cement production exceed those of the whole country. Caution is needed when interpreting the results of this ecological study. Analytical studies are necessary to document the impact of asbestos exposure on health, particularly in the future given the long latency of asbestos-related cancers.
... Nel lavoro di Corfiati et al., 22 si descrive la distribuzione dei cluster osservati, con la conferma dell'esposizione ambientale in corrispondenza dei 3 stabilimenti di cemento-amianto e dei principali poli di costruzione e riparazione navale, dove sono descritti casi nelle province di Genova e La Spezia, ma nessun caso a Gorizia o Monfalcone. Nel contributo di Marinaccio et al., 23 riguardante 514 casi con esposizione ambientale (4,3%), mentre si confermano cluster di casi associati alle 3 fabbriche del cemento-amianto, si segnalano cluster di MM connessi alla costruzione e riparazione navale, nelle sedi di Monfalcone, Trieste e La Spezia. All'impossibilità di distinguere il contributo della sola esposizione ambientale outdoor da altre indoor nei sei rapporti del ReNaM possono, in parte, rimediare i risultati del progetto collaborativo SENTIERI-ReNaM pubblicato nel 2016 24 e nel suo aggiornamento del 2019. ...
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Pleural mesothelioma clusters from outdoor environmental exposure have been highlighted also in Italy and, on the basis of epidemiological surveillance coordinated by the Italian National Mesothelioma Register, their frequency has been estimated at about 4.5%. Epidemiological studies and evaluations of some regional mesothelioma registers have made it possible to highlight that the dispersion of asbestos fibers in the outdoor environment was the only ascertained cause of mesothelioma in subjects from asbestos-cement factories, from the Balangero mine (Piedmont Region), from some serpentine rock quarries with tremolite outcrops in the Southern Apennines and in Alta Val di Susa (Piedmont Region); from chrysotile and serpentine caves in Valmalenco (Lombardy Region). Furthermore, cases of pleural mesothelioma were clearly caused by environmental pollution from fluoroedenite fibers in Biancavilla (Sicily Region). On the other hand, regional mesothelioma registers have also reported other circumstances of environmental asbestos exposure, like in the case of steel industry, shipbuilding, chemical plants, railway lines, and repair/demolition of railway carriages. However, these reports have not found confirmation on the basis of ad-hoc studies and it is likely that there is a lack of homogeneity in the assessment of individual cases. Apart from the scenarios which have been the subject of ad-hoc studies, the assessment of the causal role of environmental exposure to "in place" asbestos in the onset of pleural mesothelioma is problematic without an effort to more carefully examine the circumstances of possible exposure, harmonization of the attribution criteria used in the individual regional registers, analytical assessment of the impact of such exposure on the risk of onset of mesothelioma.
... Regarding the type of exposure, in this paper the term "anthropogenic environmental exposure" is adopted, referring to people who lived in an area with air dispersed asbestos from the asbestos-cement plant (17,18). The term "occupational exposure" refers to people who worked in contact with asbestos (19), even if, in some cases, not on a daily basis. ...
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Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.
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Malignant pleural mesothelioma (MPM) is an aggressive cancer with treatment limited to Cisplatin and Pemetrexed chemotherapy. Recently, we showed that drugs targeting the BCL-2-regulated apoptosis pathway could kill MPM cell lines in vitro, and control tumor growth in vivo. These studies showed BCL-XL was the dominant pro-survival BCL-2 family member correlating with its high-level expression in cells and patient tumor samples. In this study we show another inhibitor, AZD4320 that targets BCL-XL (and BCL-2), can also potently kill MPM tumor cells in vitro (EC50 values in the 200 nM range) and this effect is enhanced by co-inhibition of MCL-1 using AZD5991. Moreover, we show that a novel nanoparticle, AZD0466, where AZD4320 is chemically conjugated to a PEGylated poly-lysine dendrimer, was as effective as standard-of-care chemotherapy, Cisplatin, at inhibiting tumor growth in mouse xenograft studies, and this effect was enhanced when both drugs were combined. Critically, the degree of thrombocytopenia, an on-target toxicity associated with BCL-XL inhibition, was significantly reduced throughout the treatment period compared to other BCL-XL-targeting BH3-mimetics. These pre-clinical findings provide a rationale for the future clinical evaluation for novel BH3-mimetic formulations in MPM, and indeed, other solid tumor types dependent on BCL-XL.
Chapter
Malignant mesothelioma is an uncommon but lethal tumor often arising in the pleura. Traditionally, it has been associated with occupational exposure to asbestos, a group of six fibrous minerals exploited for commercial purposes and used in a myriad of industrial processes and products. After asbestos was recognized as a major risk factor for mesothelioma, protective measures and regulations for the safeguard of exposed workforces have been adopted, and commercial asbestos has been banned in many countries in recent years. However, high rates of mesothelioma due to non-occupational environmental exposure to asbestos and other fibrous minerals, such as erionite, fluoro-edenite, and vermiculite, collettively called naturally occurring asbestos (NOA), have been observed in communities living in some geographic areas with no industrial activities related to commercial asbestos over the past few decades. Asbestos and other fibrous minerals contained in Earth's crust, although inherently carcinogenic are harmless if left undisturbed. They may become airborne because of surface erosion and action altering their static nature with subsequent scattering of contaminated materials in the urban environment. Finally, residential communities living nearby industrial asbestos point sources are also at risk for environmental mesothelioma. This is known as neighborhood exposure and together with NOA makes the true environmental exposure category. The complexity of this scenario, the long latency between exposure and disease occurrence, and the lack of effective regulations for environmental asbestos contribute to hamper the adoption of efficient protective measures. This article deals with the risk and development of malignant mesothelioma due to environmental asbestos and non-asbestos mineral fibers from either commercial or non-commercial activities contaminating soil and air of geographic areas throughout the world.
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to show how malignant mesothelioma (MM) surveillance not only identifies settings of exposure representing past industrial history, but it may also detect conditions of current exposure relevant for the prevention, if the wide spectrum of asbestos uses is considered. active search of MM cases and exposure assessment at individual level through a questionnaire; identification of exposure circumstances relevant for prevention. Italy, all the Regions where a Regional Operating Centre (COR) is established to identify all MM cases diagnosed in the population and analyze their occupational, residential, household and environmental histories. Period of diagnosis: 1993-2008. descriptive analysis of MM cases and of asbestos exposures. ReNaM includes 15,845 cases of MM diagnosed between 1993 and 2008.The male/female ratio is 2.5.Mean age at diagnosis is 69 years. Pleural MMs represent 93% of all cases. Exposures have been investigated in 12,065 cases (76%). The median latency time is 46 years. In addition to clusters of MM cases in activities well known to entail asbestos use, different current exposure circumstances requiring intervention have been evidenced. on the basis of this experience, epidemiological surveillance of all occupational cancers should be implemented to foster synergies with the compensation system and the Local Health Authorities' occupational safety and health services, as required by the Italian Legislative Decree N. 81/2008.
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Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48-10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers' exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically.
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One of the most significant diseases related to environmental asbestos exposure is malignant mesothelioma (MM). Sivas province is located in the Central Anatolia where asbestos exposure is common. We aimed to study clinical, demographical and epidemiologic features of the patients with MM in Sivas, along with the history of asbestos exposure. In total, 219 patients with MM who were diagnosed in our hospital between 1993 and 2010 were retrospectively analyzed in terms of demographical and clinical features. Rock, soil and house plaster samples were taken from the habitats of those patients and were evaluated with optical microscopy and X-ray diffraction methods. The age of the patients ranged between 18 and 85 years. The male-to-female ratio was 1.4:1. Most of the patients confirmed an asbestos exposure history. The most frequent symptoms of the patients were chest pain (60 %) and dyspnea (50 %). The gap between the start of first symptoms and the diagnosis date was approximately 4 months in average. The plaster materials used in most of the houses were made up of mainly carbonate and silicate minerals and some chrysotile. Ophiolitic units contained fibrous minerals such as serpentine (clino + orthochrysotile) chiefly and pectolite, brucite, hydrotalcite and tremolite/actinolite in smaller amounts. MM is not primarily related to occupational asbestos exposure in our region, and hence, environmental asbestos exposure may be indicted. Yet, single or combined roles and/or interactions of other fibrous and non-fibrous minerals in the etiology of MM are not yet fully understood and remain to be investigated.
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Background: Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas. Aims: To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment. Methods: This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated. Results: The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984–95 period and 22 per year in the 1996–99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively). Conclusions: The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30–40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos.
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To date, no study has reported cause-specific Standardized Mortality Ratios (SMR) for asbestos-cement workers at a manufacturing establishment in Broni (Pavia, Italy). This site is among those specifically targeted by Italian Law for reclamation (SIN - Site of National Interest for remediation). To provide cause-specific SMRs for asbestos-cement workers in the Broni (Pavia, Italy) factory, with particular regard to duration of employment and latency. Cause-specific SMRs for asbestos-cement workers (1296 workers hired since 1/1/1950 and with follow-up period 1/1/1970-30/06/2004: 1254 males and 42 females, 545 deaths, 523 males and 22 females) were calculated using the cause-specific mortality rates for the Lombardy Region. Similarly, for pleural and peritoneal mesothelioma and lung cancer among male workers, SMRs by duration of employment and latency were calculated. Significantly increased SMRs were observed among male workers for pleural (SMR 17.99, 95% CI 11.75-26.36) and peritoneal (SMR 10.10, 95% CI 4.05-20.77) mesothelioma and lung cancer (SMR 1.26, 95% CI 1.02-1.55) and among female workers for pleural mesothelioma (SMR 68.90, 95% CI 8.33-248.90) and ovarian cancer (SMR 8.56, 95% CI 1.04-30.91). Only among male workers, was a significant risk trend observed for pleural mesothelioma by duration of employment and for lung cancer by latency. Significantly reduced SMRs were observed, among male workers for all causes of death, cardiovascular and respiratory diseases. The results of this cohort study showed increased SMRs for pleural and peritoneal mesothelioma and lung cancer among male workers and for pleural mesothelioma and ovarian cancer among female workers. These results are consistent with the literature data.
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Objectives: Few studies have focused on pleural mesothelioma and environmental exposure in individuals residing around an industrial source of asbestos. The aim of this study is to determine whether residential distance and wind conditions are related to the risk of developing pleural mesothelioma. Methods: In this retrospective cohort study carried out in an area of Barcelona province (Catalonia, Spain), 24 environmental pleural mesothelioma cases were diagnosed between 2000 and 2009. We calculated the age-standardised incidence rate ratios of developing this disease in the population studied, taking into account the residential distance from the plant. For cases living within a 500-m radius of the plant, the geographical location in relation to the factory was also assessed. Results: The incidence rate of environmental pleural mesothelioma was higher in the population living within 500 m of the plant than in those living in a radius of 500-2000 m and much higher than those living at 2000-10 000 m. The highest incidence rate ratio for pleural mesothelioma (161.9) was found in the southeast quadrant of the 500-m area, coinciding with the predominant wind direction. Conclusions: Residential distance from an industrial source of asbestos and local wind conditions have a considerable impact on the risk of developing environmental pleural mesothelioma.
Article
The landmark paper by Wagner et al 1 published in this journal in 1960, which linked work with crocidolite asbestos and mesothelioma in South Africa, has been instrumental in the dramatic reduction in asbestos mining and other measures to reduce asbestos exposure, most successfully in developed countries. This contrasts sharply with the lack of progress in newly industrialising countries, in particular large countries such as Brazil, China and India, which continue to produce, import and use large amounts of chrysotile asbestos. There have been several recent developments in the state of the science relating to asbestos-related cancers which have strengthened the call for more intensive action to cease asbestos mining, the manufacturing of asbestos products and to reduce exposure from existing asbestos-containing materials. In the UK, the spectrum of workers at high risk of developing mesothelioma has been changing, with a decline in those involved in mining and manufacturing and the rise in risk in carpenters, plumbers and other tradespeople, which highlights the flow-on health effects on downstream workers.2 Such findings are likely to increase the timeframe of the peak of the epidemic curve for mesothelioma, currently estimated to be within the next 10 years in Australia, where bans were …
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Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.