Concept: Asbestos and the law
Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational.
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Published over 4 years ago
On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group’s efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are being exposed in rural areas that contain noncommercial asbestos, erionite, and other mineral fibers in soil or rock (termed naturally occurring asbestos [NOA]) and are being developed. Public health authorities, scientists, residents, and other affected groups must work together in the areas where exposure to asbestos, including NOA, has been documented in the environment to mitigate or reduce this exposure. Although a blood biomarker validated to be effective for use in screening and identifying MM at an early stage in asbestos/NOA-exposed populations is not currently available, novel biomarkers presented at the meeting, such as high mobility group box 1 and fibulin-3, are promising. There was general agreement that current treatment for MM, which is based on surgery and standard chemotherapy, has a modest effect on the overall survival (OS), which remains dismal. Additionally, although much needed novel therapeutic approaches for MM are being developed and explored in clinical trials, there is a critical need to invest in prevention research, in which there is a great opportunity to reduce the incidence and mortality from MM.
Malignant mesothelioma cases among primary school teachers are usually linked with asbestos exposure due to the mineral contained in the building structure. Among the approximately 12,000 cases of mesothelioma described in the fourth report of the National Mesothelioma Register, 11 cases of primary school teachers are reported, in spite of the fact that the “catalogue of asbestos use” does not describe circumstances of asbestos exposure other than or different to that due to asbestos contained in the buildings. Four cases in the Brescia Provincial Mesothelioma Register are identified as teachers, without this circumstance of exposure.
Exposure to asbestos is causally associated with the development of malignant mesothelioma (MM), a cancer of cells lining the internal body cavities. MM is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including MM. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells that sense extracellular insults, such as asbestos, and activates a signaling cascade resulting in release of mature IL-1β and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced MM, we chronically exposed Asc-deficient mice and wild-type littermates to asbestos and evaluated differences in tumor incidence and latency. The Asc-deficient mice showed significantly delayed tumor onset and reduced MM incidence compared to wild-type animals. We also tested whether inflammation-related release of IL-1β contributes to tumor development in an accelerated mouse model of asbestos-induced MM. Nf2+/-;Cdkn2a+/- mice exposed to asbestos in the presence of anakinra, an IL-1 receptor (IL-1R) antagonist, showed a marked delay in the median time of MM onset compared to similarly exposed mice given vehicle control (33.1 weeks versus 22.6 weeks, respectively). Collectively, these studies provide evidence for a link between inflammation-related IL-1β/IL-1R signaling and the development of asbestos-induced MM. Furthermore, these findings provide rationale for chemoprevention strategies targeting IL-1β/IL-1R signaling in high risk, asbestos-exposed populations.
Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).
- Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
- Published about 6 years ago
Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.
Inhalation of asbestos and other mineral fibers are known causes of malignant mesothelioma (MM) and lung cancers. In a setting of occupational exposure to asbestos, MM occurs 4-8 times more frequently in men than in women, at the median age of 74 years, while an environmental exposure to asbestos causes the same number of MMs in men and women, at younger ages.
Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure.
The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time.
Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region, southern Italy: a national interest site for land reclamation
- Environmental science and pollution research international
- Published almost 3 years ago
Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks.