Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy

Highlights

• Higher mesothelioma rates in men (vs women) reflect higher asbestos exposure.

• Higher rates imply premature mesothelioma occurrence.

• This is the first study to evaluate rate advancement period (RAP) for mesothelioma.

• Men reached the same pleural mesothelioma incidence as women 7–10 years earlier.

• RAP is a useful measure of exposure impact also for occupational factors.

Abstract

Background

Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.

Methods

We used data from the Lombardy and Piedmont mesothelioma registries (period 2000–2016, age 45–74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).

Results

Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61–3.03) in Lombardy and 2.39 (2.17–2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).

Conclusion

Men showed more than twofold increased PM rates and reached the same incidence as women 7–10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.

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.