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Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies
  1. Francesco Barone-Adesi1,
  2. Daniela Ferrante2,
  3. Elisabetta Chellini3,
  4. Enzo Merler4,
  5. Venere Pavone5,
  6. Stefano Silvestri6,
  7. Lucia Miligi7,
  8. Giuseppe Gorini3,
  9. Vittoria Bressan4,
  10. Paolo Girardi8,
  11. Laura Ancona9,
  12. Elisa Romeo9,
  13. Ferdinando Luberto10,
  14. Orietta Sala11,
  15. Corrado Scarnato12,
  16. Simona Menegozzo13,
  17. Enrico Oddone14,
  18. Sara Tunesi2,
  19. Patrizia Perticaroli15,
  20. Aldo Pettinari15,
  21. Francesco Cuccaro16,
  22. Stefania Curti17,
  23. Antonio Baldassarre18,
  24. Tiziana Cena19,
  25. Alessia Angelini6,
  26. Alessandro Marinaccio20,
  27. Dario Mirabelli21,
  28. Marina Musti22,
  29. Roberta Pirastu23,
  30. Alessandra Ranucci24,
  31. Corrado Magnani25
  32. Working Group
    1. 1 Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy
    2. 2 Unit of Medical Statistics and Cancer Epidemiology, University of Eastern Piedmont and CPO-Piemonte, Novara, Italy
    3. 3 Environmental and Occupational Epidemiology, Cancer Prevention and Research Institute (ISPO), Firenze, Italy
    4. 4 Mesothelioma Register of the Veneto Region, Local Health Unit, Padua, Italy
    5. 5 Department of Public Health, Prevention and Security Area Work Environments, Local Health Authority, Bologna, Italy
    6. 6 Occupational Hygienist, Florence, Italy
    7. 7 Environmental and Occupational Epidemiology Unit, ISPO Cancer Prevention and Research Institute, Florence, Italy
    8. 8 Local Health Authority of Padua, Venetian Mesothelioma Registry, Padua, Italy
    9. 9 Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
    10. 10 Inter-institutional Epidemiology Unit, AUSL Reggio Emilia and Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy
    11. 11 ARPAE Emilia Romagna, Sezione Provinciale di Reggio Emilia, Reggio Emilia, Italy
    12. 12 Occupational Epidemiology, Department of Public Health, Prevention and Security Area Work Environments, Local Health Authority, Bologna, Italy
    13. 13 National Cancer Institute IRCCS Fondazione Pascale, Napoli, Italy
    14. 14 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
    15. 15 Prevention Department, ASUR Marche, Senigallia, Italy
    16. 16 Statistics and Epidemiology, Local Health Unit of Barletta-Andria-Trani, Barletta, Italy
    17. 17 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
    18. 18 Interdisciplinary Department of Medicine - Occupational Medicine 'B. Ramazzini', Università degli Studi di Bari 'Aldo Moro', Bari, Italy
    19. 19 Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
    20. 20 Occupational Medicine Department, Italian Workers’ Compensation Authority (INAIL), Rome, Italy
    21. 21 Epidemiologia dei Tumori 1, Ospedale San Giovanni Battista di Torino, Torino, Italy
    22. 22 Interdisciplinary Department of Medicine, Occupational Medicine “B. Ramazzini”, University of Bari, Bari, Italy
    23. 23 Department of Biology and Biotechnologies 'Charles Darwin', Sapienza Rome University, Rome, Italy
    24. 24 Epidemiology Unit - Department of Translational Medicine, CPO Piemonte and University of Eastern Piedmont, Turin, Italy
    25. 25 Dipartimento di Medicina Traslazionale, SCDU Epidemiologia del Tumori, Universita del Piemonte Orientale, Novara, Italy
    1. Correspondence to Professor Francesco Barone-Adesi, Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara 28100, Italy; francesco.baroneadesi{at}uniupo.it

    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.

    • epidemiology
    • mesothelioma
    • asbestos
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    Footnotes

    • Collaborators Maria Nicoletta Ballarin (previously: Mesothelioma Register of the Veneto Region, Local Health Unit, Padua, Italy), Lucia Bisceglia (Regional Health Agency of Puglia, Bari, Italy), Carol Brentisci (Unit of Cancer Epidemiology, CPO Piemonte and University of Turin, Turin, Italy), Barbara Cortini (Occupational and Environmental Epidemiology Unit - Istituto per lo Studio, la Prevenzione e la Rete oncologica (ISPRO), Florence, Italy), Stefano Mattioli (Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy), Manuela Gangemi (Unit of Cancer Epidemiology, CPO Piemonte and University of Turin, Turin, Italy), Francesco Gioffrè (previously: Mesothelioma Register of the Veneto Region, Local Health Unit, Padua, Italy), Patrizia Legittimo (formerly at Unit of Occupational Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy), Lucia Mangone (Epidemiology Unit, AUSL Reggio Emilia and IRCCS, Reggio Emilia, Italy), Francesco Marinelli (Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy), Pasqualina Marinilli (Department of Public Health, Prevention and Security Area Work Environments, Local Health Authority, Bologna, Italy), Anna Maria Nannavecchia (Regional Health Agency of Puglia, Bari, Italy), Chiara Panato (previously: Mesothelioma Register of the Veneto Region, Local Health Unit, Padua, Italy), Francesca Roncaglia (Epidemiology Unit, AUSL Reggio Emilia and IRCCS, Reggio Emilia, Italy), Cinzia Storchi (Occupational Hygienist; formerly: Regional Agency for Protection, Environment and Energy Emilia-Romagna, Provincial Office of Reggio Emilia, Italy), Antonella Stura (Unit of Cancer Epidemiology, CPO Piemonte and University of Turin, Turin, Italy), Massimo Vicentini (Occupational Hygienist; formerly: Regional Agency for Protection, Environment and Energy Emilia-Romagna, Provincial Office of Reggio Emilia, Italy), Simona Verdi (Istituto per lo Studio, la Prevenzione e la Rete oncologica (ISPRO), Florence, Italy).

    • Contributors FB-A: study design, planning and overview of data analysis, and drafting and critical revision of the article. DF: design of the study, data management, design and conduct of data analysis, and critical revision of the article. AA, MM, PP, AP, FC, SC, AB, LA, ER, FL, OS, CS, SM, EO, LM, GG, VB, VP, EM, EC: design of the study, conduct of the study and critical revision of the article. SS: exposure assessment and critical revision of the article. PG: design of the study and of data analysis and critical revision of the article. ST: data management and critical revision of the article. AR, TC: data management, data analysis and critical revision of the article. AM: design of the study, incidence data collection coordination and critical revision of the article. DM: design of the study, evaluation of exposure information and critical revision of the article. RP: design of the study, overview of mortality data analyses and critical revision of the article. CM: PI of the study, overview of the study and critical revision of the article.

    • Funding The project was partially funded by the Italian National Institute of Health - Istituto Superiore di Sanità (ISS). Asbestos Project - Ricerca corrente 2012: Progetto Amianto. The 'Casaralta' cohort study was partially funded by the Regional Government of Emilia Romagna (Resolution No 6 of the Regional Council of 18/12/2006).

    • 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.

    • Patient consent for publication Not required.

    • Ethics approval The study was approved by the University of Eastern Piedmont Ethical Review Board (Authorisation CE112/13, 12 July 2013) and to the corresponding boards of participating institutions.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No additional data are available.

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