Short communicationGender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy
Introduction
Italy was one of the main producers of chrysotile asbestos in Europe and a large consumer of all types of asbestos until 1992, when a ban was issued. Although the asbestos-related disease burden is larger for lung cancer (GBD, 2016 Risk Factors Collaborators, 2017), given the quasi-exclusive causal relationship between asbestos and malignant mesothelioma (MM), several countries established national registries or surveillance systems for MM, including Italy (Ferrante et al., 2016). Some Italian regions started registration in the early 1990s, some years before the national registry (Registro Nazionale Mesoteliomi, ReNaM) was established by law in 2002. From 1993 to 2012, ReNaM recorded 15,276 new MM cases in men (14,459 pleural mesotheliomas, PM) and 6,071 in women (5,496 PM) (Marinaccio et al., 2018b). The larger number of cases in men reflects their higher frequency and intensity of occupational exposures in most relevant economical sectors, with the exception of the asbestos and non-asbestos textile industries, where cases among women outnumber those in men (Marinaccio et al., 2018b).
Lombardy (currently 10 million inhabitants) and Piedmont (4.4 million) are two highly industrialised regions in North-Western Italy. Piedmont, in which the largest Italian asbestos-cement factory has been operating (in Casale Monferrato), was one of the first regions to implement a MM registry (1990), while Lombardy (which hosted the second largest factory, in Broni) started in 2000. The number of cases of MM due to past exposure to asbestos is particularly high in these two regions (Mensi et al., 2016, 2016b, 2017; Mirabelli et al., 2007). In recent years (2010–2014), about 40% of all Italian MM cases (>1600/year) were recorded in Lombardy (>400/year) and Piedmont (>200/year) (Marinaccio et al., 2018a).
Relative measures of association, such as rate ratios (RR), describe the strength of the disease-exposure association, while absolute measures like rate differences and related measures (such as the attributable fractions and risks/rates) are used to quantify the public health impact of exposures. A further measure has been described, the rate advancement period (RAP), which assesses the time by which disease rates are advanced among exposed (or more exposed) subjects. Therefore, the focus of RAP is on premature disease occurrence. For this reason, RAP is thought to be more understandable to lay people and hence more useful in individual risk communication (Brenner et al., 1993; Discacciati et al., 2016).
Examples of RAP estimation using published data have been provided in the paper that proposed the method (Brenner et al., 1993). Subsequently, RAP has been used to assess the impact of various risk determinants on several diseases. In a cohort study in Germany hypertension, smoking, and dyslipidemia were associated with RAPs of 8, 11, and 11 years, respectively (Liese et al., 2000). In another German study on smoking and overall mortality, current smokers showed a 2.5-fold increased risk for all-cause mortality compared with never smokers, corresponding to a RAP of 10.7 years (Gellert et al., 2013). A cohort study in Ontario, Canada estimated a hazard ratio of 1.18 for subjects living close to major roads and a corresponding RAP of 2.5 years, while RAPs for chronic pulmonary disease, chronic ischemic heart disease, and diabetes were 3.4, 3.1, and 4.4 years, respectively (Finkelstein et al., 2004). A recent study evaluated RAP for alcohol use and overall and cause-specific mortality in the large EPIC (European Prospective Investigation into Cancer and nutrition) cohort (Ferrari et al., 2014). Finally, two meta-analysis studies within CHANCES (Consortium on Health and Aging: Network of Cohorts in Europe and the United States), used RAP to estimate the impact of smoking and smoking cessation on cardiovascular diseases (Mons et al., 2015), and of smoking on various cancer sites (Ordonez-Mena et al., 2016). To our knowledge, RAP has never been used to evaluate premature occurrence of asbestos-related diseases and in occupational settings in general.
Using Lombardy and Piedmont data on PM incidence from 2000 to 2016 we compared men and women by calculating the age-adjusted RR as a measure of association and RAP as a measure of impact to quantify the time (age) by which the rate in men (historically more exposed to asbestos) reach the same rate as women.
Section snippets
Cases and population data
The Lombardy and Piedmont MM Registries have been described in detail elsewhere (Mensi et al., 2016; Mirabelli et al., 2007). Briefly, they collect clinical information on newly diagnosed MM cases occurring among residents from regional and extra-regional hospitals. Diagnosis is evaluated on individual basis and classified according to ReNaM guidelines as “definite” (histological diagnosis, possibly with immuno-histochemical confirmation), “probable” (usually, cytology plus imaging), or
Results
In the years 2000–2016, 5842 PM cases (3836 men, 2006 women) were recorded by the Lombardy registry and 3644 (2370 men, 1274 women) by the Piedmont registry (Table 1). The average crude incidence rates (per 10,000 person-years) were 4.8 (men) and 2.4 (women) in Lombardy and 6.6 (men) and 3.3 (women) in Piedmont. Mean age at diagnosis was lower in men than in women (3.0 years less in Lombardy and 1.6 in Piedmont). The majority of male cases (62.7% in Lombardy and 58.6% in Piedmont) had 45–74
Discussion
In this study, we applied for the first time RAP to mesothelioma data to evaluate the effects of past asbestos exposures. We found that the higher asbestos exposure in men, compared to women, translated into a substantial advancement in the age of development of PM. We estimated in both regions that men reach the same PM rates as women roughly between 7 and 10 years earlier (with higher advancement at older ages).
This study was based on a virtually complete series of cases with good evidence of
Conclusions
In this study we showed that, compared to women, more frequent and more intense asbestos exposures in men translates in an advancement of 7–10 years in mesothelioma occurrence. Measures of disease advancement (premature disease occurrence) like RAP can effectively describe the impact on population health of a specific exposure and may usefully integrate traditional epidemiological measures in risk communication.
Authors contribution
Dario Consonni conceived the study, performed statistical analysis, and drafted the manuscript. Franceso Barone-Adesi, Sara De Matteis, Enrico Oddone, Angela C Pesatori, contributed to interpretation and discussion of results. Dario Mirabelli, Enrica Migliore, Barbara Dallari, Luciano Riboldi, Carolina Mensi participated in data collection, clinical and exposure evaluation, and contributed to interpretation and discussion of results. All authors read and approved the final manuscript.
Funding source
This work was partially supported by: Ministry of Health, CCM (Centro Nazionale per la Prevenzione e il Controllo delle Malattie), Rome, Italy; Istituto Nazionale per l’Assicurazione contro gli Infortuni sul Lavoro (INAIL), Rome, Italy: BRiC P55 and P59; Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy: IG 2015/17692.
Conflicts of interest
Dario Consonni and Carolina Mensi served as consultants for the court in trials concerning asbestos-related diseases. Dario Mirabelli, Francesco Barone-Adesi, and Enrico Oddone served as expert witness for the public prosecutor in trials concerning asbestos-related diseases.
Approval
As reporting of malignant mesothelioma to the National Mesothelioma Registry (ReNaM) is compulsory by law (277/1991 and 81/2008), ethics approval is not required.
Acknowledgements
The authors wish to thank the personnel of the regional hospital Occupational Health Departments (UOOML) and of the Occupational Prevention and Safety Departments of the Local Health Units (SPSAL) for their collaboration in notifying and interviewing subjects affected by mesothelioma; the personnel of the regional hospital Medical, Surgical, and Pathology Departments for their collaboration in providing clinical documentation; Luana Garlati, Lombardy Mesothelioma Registry, for her valuable
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