Asbestos ban policies and mesothelioma mortality in Greece

Our findings confirm that men are considerably more affected by mesothelioma than women, with a male:female ratio of 3:1. The WHO mortality database, which included data on mesothelioma deaths from 1994 to 2008, also found a roughly similar ratio [26]. This ratio supports the notion that the disease primarily affects men because is caused by occupational asbestos exposure [41]. Environmental asbestos exposure has a similar impact on both genders and the ratio of male to female will not change noticeably. The male-to-female ratio varies with different types of exposure, mainly occupational. Areas with occupational sectors where workers are exposed to asbestos may have a higher male-to-female ratio, if these workers were primarily men. Women may have a higher prevalence of familial asbestos exposure (when a member of their family has occupational exposure to asbestos) [42‐45]. A study suggested that the risk of MM in females is comparable to that of males, and more thorough exposure histories for females are required [46].

According to our study, mesothelioma typically affects adults within the age group of 60 and 79. This finding is supported by other studies and is compatible with the lengthy latent period of the disease [31, 47]. Mazureck et al. suggested that the majority of MM deaths, between 1999 and 2015 in the USA, occurred in both sexes between the ages of 75 and 84 [48]. A study conducted between 2005 and 2015 in southern Italy, where there was environmental exposure to ophiolite, revealed that the average age of MM deaths ranged from 65 to 77 years [42]. Data from the WHO mortality database, covering the period from 1994 to 2008, showed the average age of mesothelioma deaths was 70 years old [49].

Regardless of the gender, mesothelioma mortality rates in Greece have been rising from 1983 to 2019. This period was divided into three sub-periods 1983–1999, 2000–2009, and 2010–2019, in order to revealing the trend of MM deaths. The age-standardized mortality rates for males, and the general population doubled over the past two sub-periods, and there was a substantial increase among the three sub-periods (p < 0.001). The age-standardized mortality rates for females increased among the first and third sub-period (p < 0.01). The joinpoint analysis supported a slight but persistent rise in Females’s as well as a significant progressive increase in males’ and the overall population’s confirmed ASMRs. This increased ASMR is a result of asbestos use and production in Greece over the 20th century. Asbestos production in Greece began in the 1960s, and it grew from 1970 onward, reaching a peak in the 1990s Greek asbestos manufacturing peaked in 1996 and ceased in 1999, while asbestos exports continued until 2003 [25]. Domestic use of asbestos in Greece accounted for 20–25% of production in 1980, and a significant asbestos consumption rate of 1.9 kg/person was recorded in 1986 [25, 28]. By 1993, 95% of the fiber had been exported, and in 2005 Greece passed legislation forbidding the usage of all types of asbestos [10, 25, 28]. Based on the above data, we can conclude that there was significant asbestos production and consumption in Greece up to the mid-1990s. Given the long latent period of mesothelioma, an increase in the number of deaths from mesothelioma and consequently the ASMR in Greece during the early decades of the 21st century is anticipated. As the latent period of mesothelioma and their relation with the incidence of mesothelioma is concerned, there were several studies referred to a minimum latent period of 10 years, and other cohort studies with a maximum follow-up of 40 years after the initial asbestos exposure showed that the incidence of MM increased continuously over time after exposure, with no upper limit [50‐54]. However, more recent cohort studies, that include longer periods of observation (for 50 years or longer), showed an attenuation of the pleural MM risk increase and a continuing increase for peritoneal MM [55]. Additionally, incidence trend analysis revealed that the rate of growth in incidence is reducing, especially in the countries that implemented earlier asbestos bans or reduction programs. This change is more pronounced in younger age groups exposed to lower levels of asbestos [28].

Except for the use and production of asbestos in Greece, the advancements in diagnostic techniques may have contributed to the rise in ASMRs between the three study periods (1983–1999, 2000–2009, and 2010–2019). Since mesothelioma knowledge and diagnosis have improved, there may be an association between the rising mortality rates and the increased incidence reports. The rule banning all forms of asbestos was just put into effect a short time ago in Greece, therefore it’s not surprising that ASMR has continued to rise.

The incidence and mortality mesothelioma rates are consistent with trends in asbestos exposure due to the strong causal link between asbestos and mesothelioma [28]. Studies have revealed that the time of the law’s implementation prohibiting the use of asbestos has an impact on these rates as well [10, 29‐31]. MM incidence trends differ between European nations. The peak incidence of mesothelioma in Finland was reported to have occurred in 2006, and this country was one of the first in Europe to implement a law outlawing the use of asbestos early in 1992 [31]. Moreover, Sweden was among the first nations in the world where the incidence of MPM began to decline very early in 1995 [31]. Although MM mortality in the Netherlands was predicted to peak around 2020, a recent analysis suggested that MM incidence peaked earlier in 2010 [29, 56, 57]. The Netherlands was one of the countries with high rates of MM and an early national asbestos ban in 1993 [29]. Despite the early implementation of the asbestos ban law in Italy in 1992, a recent study predicts that the incidence of ARDs(Asbestos Related Diseases) will reach its peak in 2021 [28, 58]. This was attributed to the prolonged latent period of ARDs, as well as exposure to asbestos-containing products and/or environmental exposure brought on by living near sources of asbestos-like natural fibers or polluted locations [58, 59].

During the 1970s, there has been a significant decrease in occupational asbestos exposure in the USA, which resulted in a consistent decrease in MPM (Malignant Pleural Mesothelioma) incidence after 2000. Particularly, the drop was significantly higher in males than in females, with the highest MPM incidence being found in 2000 and the lowest in 2016 [30]. Australia had the largest per-capita asbestos usage, which peaked in the 1970s, and a complete ban on asbestos in 2003 [60]. The incidence rates of MM in Australia have stabilized over the first decade of the 21st century (2.8 per 100,000 in 2011) [60]. According to a research, the crude mesothelioma mortality rate has been rising in Brazil for both males and females and it’s important to mention that Brazil was one of the top four asbestos producers in 2020 [61].

Regardless of gender, the annual ASMR progressively increased from 1983 to 2019 in Greece. A closer study revealed that the rates for males and the whole population had peaked in 2011, but the ASMRs for females were still rising until 2019. The ASMRs for males and the total population were high but constant over the second decade of the 21st century, remaining below the values they had in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). These rates stabilized about 15 years after the peak of asbestos production and use in Greece, which was around in the middle of the 1990s. This stability is concerning for male’s ASMRs since the incidence of mesothelioma in men is associated with occupational asbestos exposure. In many countries, where the ASMRs for males have decreased or stabilized, the ASMR for females has continued to rise or remained more stable [10, 30, 48]. The data that is available now supports the theory that elevated female mortality rates are mostly caused by non-occupational exposure, particularly family exposure (secondary exposure when a family member is exposed to asbestos at work), which causes MM in women [62]. Additionally, it has been documented that mesothelioma is causally connected with germline mutations of BRCA1-associated protein 1 (BAP1) and various tumour suppressor genes [63]. Mesotheliomas associated with inherited germline mutations have a M:F ratio that is about 1:1 and manifest at a younger age similar to those resulting from environmental exposure [63‐68]. Recent research on survival rates revealed that individuals with germline BAP1 mutations and women with malignant pleural mesothelioma have better survival rates than males [69, 70]. In terms of genetic susceptibility, MM is often diagnosed three or more decades after the asbestos exposure first occurs, but the precise genetic and molecular changes that occur during this time are still unknown. Furthermore, there is controversy on the proportion of MM cases worldwide that can be linked to genetic susceptibility. According to the present study, it is extremely positive that the annual ASMR for males and the whole population has stabilized since 2011, even though the mean ASMR in the most recent studied period (2010–2019) was double that of the previous period (2000–2009) regardless of gender.

During the most recent period 2010–2019, regional ASMRs rose in all areas of Greece except for Epirus. We found that ASMRs were significantly higher in Attiki (P < 0.01) and a sizable increase in Sterea Ellada and Macedonia-Thraki. It is important to note that one of the major asbestos factories, which was in operation until the middle of the 1990s, was situated in Nea Lampsako in Evia, which is part of Sterea Ellada and is near to Attiki [25]. Furthermore, the greatest asbestos deposit was in Zidani, a region in the county of Kozani, which is located in Macedonia. The asbestos mining there started in the 1970s and reached its peak in 1996 [25]. The significant increase in ASMRs in regions of Attiki, Sterea-Ellada, and Macedonia-Thraki is anticipated to occur not only in the second but also in the third decade of the 21st century, as there were the main asbestos-factories in Greece operated until 1999.

The decline in ASMR in Epirus from 0.54/100000person-years (2000–2009) to 0.31/100000person-years (2010–2019) is both noteworthy and encouraging. According to our previous research, the highest MMR in Epirus occurred between 1983 and 2003, and this rate stabilized in the period 2004–2015 [36]. At this point, we would like to highlight that Metsovo is a city in the region of Epirus, where a high prevalence of an endemic condition known as “Metsovo lung”—calcification of the pleura—was discovered before 1980 [39]. Since 1969, it has been widely known that Metsovo inhabitants whitewashed their interior walls with asbestos-contaminated soil, called “luto” in the local dialect. Bazas et al. and Konstantopoulos et al. revealed the health problems associated with “luto” in the 1980s, including pleural diseases [38, 39]. Following the implementation of a health promotion strategy, the “luto” has not been used since 1985, putting an end to the epidemic of domestic exposure [71]. According to previously published data, the MMR in Epirus was the highest in Greece before 2000, then it stabilized and recently decreased as a result of the improved surveillance, and a further decline in rate is predicted for the following years [35, 36]. The intriguing discovery of a lower ASMR in Epirus emphasizes the need of raising awareness of the condition and putting effective public health measures into practice. Therefore, it is crucial to implement a Registry for the MM incident cases so as to successfully monitor MM in Greece.