Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register
Introduction
Malignant mesothelioma (MM) is a lethal tumour which arises from the serosal coverings of the pleura and, less frequently, of the pericardial and peritoneal cavities and from the tunica vaginalis of the testis. The relationship with asbestos exposure has been definitely demonstrated, but some aspects of biological mechanisms by which asbestos causes MM are still under scrutiny.1 Latency time for MM shows a great variability and the relationship with the asbestos exposure intensity (and duration) is still not clarified. The range of latency period in the published study is exceptionally extensive and MM cases with a latency period shorter than 10 years are very rare. Some authors reported that latency has increased during the time due to less heavy exposure conditions,2 but this remains a controversial issue.3 Data regarding the influence of dose-response on latency are not frequent and there is no evidence about the putative role of other factors such as tumour site, asbestos fibre types and morphology.4, 5, 6, 7
Italy was an important producer of raw asbestos until its ban in 1992. In-house production peaked at more than 160,000 tons/year between 1976 and 1979, then it went on with more than 100,000 tons/year up to 1987; additionally, importation exceeded in-house production from 1989 to 1991 (more than 60,000 tons/year). Italy is now experiencing severe public health consequences due to large-scale industrial use of asbestos, as it was extensively used in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and other industrial sectors. In 2001, 797 men and 380 women deceased from pleural tumours and the national standardised mortality rate was 2.45 and 1.11 (×100,000 inhabitants) among men and women respectively. Historical Italian asbestos consumption curves and current MM mortality trends make a decrease of MM deaths in future years unpredictable.8, 9
Since 1993, the National Mesothelioma Registry (ReNaM) has carried out a permanent MM epidemiologic surveillance, recently publishing figures for incidence, survival and asbestos exposure.10, 11, 12
The aim of the present study is to estimate the latency period (and its variability) in the large MM case list collected by ReNaM. The correlation between latency length and the modalities of asbestos exposure (professional, environmental or at leisure) are investigated, as well as the putative influence on latency of demographic and diagnostic factors (age at diagnosis, gender, anatomical site, cancer morphology, level of diagnostic certainty and incidence period).
Section snippets
Methods
ReNaM has a regional structure: a Regional Operating Centre (COR) has been progressively established in 18 Italian regions (out of 21) and one province, nowadays attaining coverage of almost the entire national territory (98.5% of the Italian population). Each COR acts independently applying standardised methods established by national guidelines. CORs collect incident malignant mesothelioma cases from health care institutions that diagnose and treat cases of mesothelioma (especially pathology
Results
The ReNaM dataset included 5173 new MM cases diagnosed during the period 1993–2001. Applying the selection criteria described above, 2544 patients (49.2%) came out to be eligible for latency analysis. The general characteristics of this cohort are reported in Table 1. Mean latency was 44.6 years (CI 95% 44.1–45.0), with a standard deviation of 12 years and a Gaussian distribution around the mean. The distribution of mean latency by anatomical site and gender is reported in Table 2. Among
Discussion
It is widely agreed that mesothelioma latency is very long (up to 40 years and more) and with a great range of variability, but analyses of case lists from large national population-based registers are not frequently reported. The discussion on mesothelioma latency is a relevant issue considering the still unclear process of cancer causation from asbestos fibre inhalation13 and the lack of encouraging progress in mesothelioma treatments.14 Moreover, any prediction about the future burden of
Conflict of interest statement
None declared.
Acknowledgement
The authors thank Dr. Patrizia Scano for her support in linguistic revision of the text.
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ReNaM Working Group: Tosi S, Branchi C (ISPESL), Convertini L (COR Basilicata), Bianchelli M, Benfatto L, Lazzarotto A, Viarengo P (COR Liguria), Seniori-Costantini A, Badiali A, Cacciarini V, Chellini E, Silvestri S (COR Toscana), Menegozzo S, Izzo F (COR Campania), Riboldi L, Pesatori AC (COR Lombardia), Gioffrè F, Ballarin N, Roberti S (COR Veneto), Bertolotti M, Stura A, Gangemi M, Merletti F (COR Piemonte), Pascucci C (COR Marche), Candela S, Mangone L, Pezzarossi A, Storchi C (COR Emilia-Romagna), Scondotto S, Cianciolo G, Nicita C, Dardanoni G, Di Giorgi M, Miceli G, Mira A (COR Sicilia).