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      Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden

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          Abstract

          Background

          We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.

          Methods

          Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.

          Results

          Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).

          Conclusions

          The approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.

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          Most cited references23

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          Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma

          The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.
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            The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.

            Mortality reports on asbestos exposed cohorts which gave information on exposure levels from which (as a minimum) a cohort average cumulative exposure could be estimated were reviewed. At exposure levels seen in occupational cohorts it is concluded that the exposure specific risk of mesothelioma from the three principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite respectively. For lung cancer the conclusions are less clear cut. Cohorts exposed only to crocidolite or amosite record similar exposure specific risk levels (around 5% excess lung cancer per f/ml.yr); but chrysotile exposed cohorts show a less consistent picture, with a clear discrepancy between the mortality experience of a cohort of xhrysotile textile workers in Carolina and the Quebec miners cohort. Taking account of the excess risk recorded by cohorts with mixed fibre exposures (generally<1%), the Carolina experience looks uptypically high. It is suggested that a best estimate lung cancer risk for chrysotile alone would be 0.1%, with a highest reasonable estimate of 0.5%. The risk differential between chrysotile and the two amphibole fibres for lunc cancer is thus between 1:10 and 1:50. Examination of the inter-study dose response relationship for the amphibole fibres suggests a non-linear relationship for all three cancer endpoints (pleural and peritoneal mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is proportional to the square of cumulative exposure, lung cancer risk lies between a linear and square relationship and pleural mesothelioma seems to rise less than linearly with cumulative dose. Although these non-linear relationships provide a best fit ot the data, statistical and other uncertainties mean that a linear relationship remains arguable for pleural and lung tumours (but not or peritoneal tumours). Based on these considerations, and a discussion fo the associated uncertainties, a series of quantified risk summary statements for different elvels of cumulative exposure are presented.
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              Epidemiology of peritoneal mesothelioma: a review.

              P Boffetta (2007)
              The epidemiology of peritoneal mesothelioma is complicated by possible geographic and temporal variations in diagnostic practices. The incidence rates in industrialized countries range between 0.5 and three cases per million in men and between 0.2 and two cases per million in women. Exposure to asbestos is the main known cause of peritoneal mesothelioma. Results on peritoneal mesothelioma have been reported for 34 cohorts exposed to asbestos, among which a strong correlation was present between the percentages of deaths from pleural and peritoneal mesothelioma (correlation coefficient 0.8, P < 0.0001). Studies of workers exposed only or predominantly to chrysotile asbestos resulted in a lower proportion of total deaths from peritoneal mesothelioma than studies of workers exposed to amphibole or mixed type of asbestos. Cases of peritoneal mesothelioma have also been reported following exposure to erionite and Thorotrast, providing further evidence of common etiological factors with the pleural form of the disease. The role of other suspected risk factors, such as simian virus 40 infection and genetic predisposition, is unclear at present. Control of asbestos exposure remains the main approach to prevent peritoneal mesothelioma.
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                Author and article information

                Journal
                Occup Environ Med
                Occup Environ Med
                oemed
                oem
                Occupational and Environmental Medicine
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1351-0711
                1470-7926
                May 2016
                29 December 2015
                : 73
                : 5
                : 290-299
                Affiliations
                [1 ]London School of Hygiene and Tropical Medicine , London, UK
                [2 ]Health and Safety Laboratory , Buxton, UK
                [3 ]Department of Histopathology, Royal Brompton and Harefield Hospitals NHS Foundation Trust, and National Heart and Lung Institute, Imperial College , London, UK
                [4 ]Department of Cellular Pathology, Leeds Teaching Hospitals NHS Trust , Leeds, UK
                [5 ]Medical Research Council Clinical Trials Unit, Kingsway , London, UK
                [6 ]Health and Safety Executive , Bootle, UK
                Author notes
                [Correspondence to ] Clare Gilham, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; clare.gilham@ 123456lshtm.ac.uk
                Article
                oemed-2015-103074
                10.1136/oemed-2015-103074
                4853597
                26715106
                e6bc6527-b7ce-4635-8b05-df6063e953bc
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

                History
                : 16 May 2015
                : 20 October 2015
                : 11 November 2015
                Categories
                1506
                Exposure Assessment
                Original article
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                Occupational & Environmental medicine
                Occupational & Environmental medicine

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