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1. Cause specific mortality in an Italian pool of asbestos workers cohorts.

Author

Ferrante D, Angelini A, Barbiero F, Barbone F, Bauleo L, Binazzi A, Bovenzi M, Bruno C, Casotto V, Cernigliaro A, Ceppi M, Cervino D, Chellini E, Curti S, De Santis M, Fazzo L, Fedeli U, Fiorillo G, Franchi A, Gangemi M, Giangreco M, Rossi PG, Girardi P, Luberto F, Massari S, Mattioli S, Menegozzo S, Merlo DF, Michelozzi P, Migliore E, Miligi L, Oddone E, Pernetti R, Perticaroli P, Piro S, Addario SP, Romeo E, Roncaglia F, Silvestri S, Storchi C, Zona A, Magnani C, and Marinaccio A

Subjects
Male, Humans, Female, Cause of Death, Cohort Studies, Construction Materials, Italy epidemiology, Mesothelioma etiology, Occupational Exposure adverse effects, Occupational Diseases etiology, Asbestos adverse effects, Pleural Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Lung Neoplasms etiology
Abstract

Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers., Methods: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period., Results: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter., Conclusions: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Published
2024
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2. Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

Author

Azzolina D, Consonni D, Ferrante D, Mirabelli D, Silvestri S, Luberto F, Angelini A, Cuccaro F, Nannavecchia AM, Oddone E, Vicentini M, Barone-Adesi F, Cena T, Mangone L, Roncaglia F, Sala O, Menegozzo S, Pirastu R, Tunesi S, Chellini E, Miligi L, Perticaroli P, Pettinari A, Bressan V, Merler E, Girardi P, Bisceglia L, Marinaccio A, Massari S, and Magnani C

Subjects
Humans, Cohort Studies, Italy epidemiology, Mortality trends, Risk Assessment, Male, Female, Construction Industry, Adult, Middle Aged, Aged, Asbestos toxicity, Lung Neoplasms epidemiology, Lung Neoplasms mortality, Mesothelioma epidemiology, Mesothelioma mortality, Occupational Diseases epidemiology, Occupational Diseases mortality, Occupational Exposure adverse effects, Pleural Neoplasms epidemiology, Pleural Neoplasms mortality
Abstract

Introduction: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy., Method: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE)., Result: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE., Conclusion: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality., Competing Interests: Competing interests: The authors declare that they have no competing interests. The following authors or working group components reported that they served as expert witness in court trials on asbestos related diseases: AA, AB, CM, DM, EM, EO, FB-A, LBi, LMa, LMi, MM, SMe, SS, VP., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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3. Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

Author

Barone-Adesi F, Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L, Gorini G, Bressan V, Girardi P, Ancona L, Romeo E, Luberto F, Sala O, Scarnato C, Menegozzo S, Oddone E, Tunesi S, Perticaroli P, Pettinari A, Cuccaro F, Curti S, Baldassarre A, Cena T, Angelini A, Marinaccio A, Mirabelli D, Musti M, Pirastu R, Ranucci A, and Magnani C

Subjects
Adolescent, Adult, Female, Humans, Italy epidemiology, Male, Middle Aged, Models, Theoretical, Time Factors, Young Adult, Asbestos adverse effects, Occupational Diseases mortality, Occupational Exposure adverse effects, Peritoneal Neoplasms mortality, Pleural Neoplasms mortality
Abstract

Objectives: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis., Methods: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time., Results: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer., Conclusions: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations., Competing Interests: Competing interests: SM served as expert witness for the judge, the public prosecutor and the defendant’s attorneys in court trials regarding asbestos-related diseases. CM and SS served as expert witnesses for the judge and the public prosecutor in court trials regarding asbestos-related diseases. AA, FB-A, PL, EM, LMi, DM and EO served as expert witnesses for the public prosecutor in court trials regarding asbestos-related diseases. LMa conducted negotiations and stipulated contracts representing the Italian Association of Cancer Registries (AIRTUM) for the preparation and publication of specific reports on the epidemiology of tumour pathologies with MSD, Lilly and Sanofi. All other authors declare they have no actual or potential competing financial interests., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2019
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4. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.

Author

Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L, Gorini G, Bressan V, Girardi P, Ancona L, Romeo E, Luberto F, Sala O, Scarnato C, Menegozzo S, Oddone E, Tunesi S, Perticaroli P, Pettinari A, Cuccaro F, Mattioli S, Baldassarre A, Barone-Adesi F, Cena T, Legittimo P, Marinaccio A, Mirabelli D, Musti M, Pirastu R, Ranucci A, and Magnani C

Subjects
Adult, Aged, Asbestosis mortality, Carcinogens, Cause of Death trends, Cohort Studies, Construction Materials, Female, Humans, Italy epidemiology, Lung, Lung Neoplasms etiology, Male, Mesothelioma etiology, Mesothelioma, Malignant, Middle Aged, Occupational Diseases etiology, Ovarian Neoplasms etiology, Ovary, Peritoneal Neoplasms etiology, Peritoneum, Pleura, Pleural Neoplasms etiology, Asbestos adverse effects, Lung Neoplasms mortality, Mesothelioma mortality, Occupational Diseases mortality, Occupational Exposure adverse effects, Ovarian Neoplasms mortality, Peritoneal Neoplasms mortality, Pleural Neoplasms mortality
Abstract

Objective: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers., Methods: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period., Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after., Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports., Competing Interests: Competing interests: The following authors reported that they served as expert witness for the public prosecutor in court trials on asbestos related diseases: CM, EM, DM, EO, SS., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Published
2017
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5. Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure

Author

Magnani C., Silvestri S., Angelini A., Ranucci A., Azzolina D., Cena T., Chellini E., Merler E., Pavone V., Miligi L., Gorini G., Bressan V., Girardi P., Bauleo L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Mattioli S., Baldassarre A., Barone-Adesi F., Musti M., Mirabelli D., Pirastu R., Marinaccio A., Massari S., Ferrante D, Working Group, Ballarin MN, Brentisci C, Cortini B, Curti S, Gangemi M, Gioffrè F, Legittimo P, Mangone L, Marinelli F, Marinilli P, Panato C, Roncaglia F, Storchi C, Stura A, Vicentini M, Verdi S, Nannavecchia AM, Bisceglia L, Magnani C., Silvestri S., Angelini A., Ranucci A., Azzolina D., Cena T., Chellini E., Merler E., Pavone V., Miligi L., Gorini G., Bressan V., Girardi P., Bauleo L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Mattioli S., Baldassarre A., Barone-Adesi F., Musti M., Mirabelli D., Pirastu R., Marinaccio A., Massari S., Ferrante D, Working Group, Ballarin MN, Brentisci C, Cortini B, Curti S, Gangemi M, Gioffrè F, Legittimo P, Mangone L, Marinelli F, Marinilli P, Panato C, Roncaglia F, Storchi C, Stura A, Vicentini M, Verdi S, Nannavecchia AM, and Bisceglia L

Subjects
Risk, Mesothelioma, Lung Neoplasms, Pleural Neoplasms, Socio-culturale, Asbesto, Cohort Studies, Cause of Death, Occupational Exposure, Asbestos, Glassworks, Rolling stock, Shipyards, Humans, Industry, Peritoneal Neoplasms, Retrospective Studies, Mineral Fibers, Ovarian Neoplasms, Construction Materials, Ambientale, Italy, Urinary Bladder Neoplasms, Asbestosis, Glasswork, Female
Abstract

Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers.Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period.The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer.The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

Published
2020

6. Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies

Author

Barone-Adesi F., Ferrante D., Chellini E., Merler E., Pavone V., Silvestri S., Miligi L., Gorini G., Bressan V., Girardi P., Ancona L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Curti S., Baldassarre A., Cena T., Angelini A., Marinaccio A., Mirabelli D., Musti M., Pirastu R., Ranucci A., Magnani C., Working Group, Mattioli S., Barone-Adesi F., Ferrante D., Chellini E., Merler E., Pavone V., Silvestri S., Miligi L., Gorini G., Bressan V., Girardi P., Ancona L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Curti S., Baldassarre A., Cena T., Angelini A., Marinaccio A., Mirabelli D., Musti M., Pirastu R., Ranucci A., Magnani C., Working Group, and Mattioli S.

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Time Factors, Time Factor, Adolescent, Pleural Neoplasms, asbestos, epidemiology, mesothelioma, Asbesto, medicine.disease_cause, Asbestos, Settore MED/01 - Statistica Medica, NO, 03 medical and health sciences, Peritoneal Neoplasm, Young Adult, 0302 clinical medicine, Internal medicine, Occupational Exposure, Epidemiology, medicine, Humans, Pleural Neoplasm, Mesothelioma, Young adult, Peritoneal Neoplasms, business.industry, Public Health, Environmental and Occupational Health, Cancer, asbestos, epidemiology, mesothelioma, Adolescent, Adult, Italy, Middle Aged, Models, Theoretical, medicine.disease, 030210 environmental & occupational health, Occupational Disease, Occupational Diseases, asbestos, epidemiology, mesothelioma, Italy, 030220 oncology & carcinogenesis, Female, business, Human, Cohort study
Abstract

ObjectivesModels based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.MethodsWe used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.ResultsRates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.ConclusionsRates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Published
2019

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