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Downloaded from oem.bmjjournals.com on 16 September 2005 Are lung and pleural benign asbestos induced diseases a preliminary step in the pathogenic process of mesothelioma and lung cancer development? M Goldberg Occup. Environ. Med. 2005;62;663-664 doi:10.1136/oem.2005.021865 Updated information and services can be found at: http://oem.bmjjournals.com/cgi/content/full/62/10/663 References These include: This article cites 11 articles, 3 of which can be accessed free at: http://oem.bmjjournals.eom/cgi/content/full/62/10/663#BIBL Rapid responses Email alerting service You can respond to this article at: http://oem.bmjjournals.com/cgi/eletter-submit/62/10/663 Receive free email alerts when new articles cite this article - sign up in the box at the top right corner of the article Topic collections Articles on similar topics can be found in the following collections Occupational Health (1074 articles) Other respiratory medicine (913 articles) Other Epidemiology (1411 articles) Cancer:other (865 articles) Notes To order reprints of this article go to: http://www.bmjjournals.com/cgi/reprintform To subscribe to Occupational and Environmental Medicine go to: http://www.bmjjournals.com/subscriptions/ Downloaded from oem.bmjjournals.com on 16 September 2005 664 COMMENTARY the common cause without interac tion hypothesis for peritoneal mesothe lioma. On the other hand, benign chest diseases may also have been underestimated, either because they appeared only after the initial radio graphic examination at the inclusion of the subjects in the cohort, or because they were too small to be apparent using conventional radio graphic techniques. The question of the mechanisms of asbestos induced cancers still remains open. It is of great importance to clarify further this question for scientific rea sons, but also because the single sequential pathogenic process hypoth esis is taken for granted in countries that compensate asbestos induced dis eases only in cancer patients that exhibit chest abnormalities. Occup Environ Med 2005;62:663-664. doi: 10.1136/oem.2005.021865 Correspondence to: Prof. M Goldberg, Inserm Unite o87-IFR 69, 14 rue du Val d'Osne, 94410 Saint Maurice, France; marcel.goldberg@st-maurice.inserm.fr Competing interests: none declared REFERENCES 1 Peto J, Decarli A, La Vecchia C, et al. The European mesothelioma epidemic. Br J Cancer 1999;79:666-72. 2 Goldberg M. Amiante: I'epidemiologie a-t-elle encore un avenir? Rev Epidemiol Sante Publ 2001;49:505-11. 3 INSERM. Effets sur la sante des principaux types d'exposition a I'amiante. Paris: Editions INSERMCollection Expertises Collectives, 1997. 4 Collier CG, Morris KJ, Launder KA, The behavior of glass fibers in the rat following peritoneal injection, et al. Regul Toxicol Pharmacol 1994;20:S89-103. 5 McConnell EE. Synthetic vitreous fibers inhalation studies. Regul Toxicol Pharmacol 1994;20:S22-34. 6 Weiss WMD. Asbestos-related pleural plaques and lung cancer. Chest 1993;103:1854-9. 7 Hillerdal G. Pleural plaques and risk for bronchial carcinoma and mesothelioma. A prospective study. Chest 1994;105:144-50. 8 Bianchi C, Brollo A, Ramani L, et al. Pleural plaques as risk indicators for malignant pleural mesothelioma: a necropsy-based study. Am J Ind Med 1997;32:445-9. 9 Karjalainen A, Pukkala E, Kauppinen T, et al. Incidence of cancer among Finnish patients with asbestos-related pulmonary or pleural fibrosis. Cancer Causes Control 1999;10:51-7. 10 Koskinen K, Pukkala E, Martikainen R, et al. Different measures of asbestos exposure in estimating risk of lung cancer and mesothelioma among construction workers. J Occup Environ Med 2002;44:1190-6. 11 Wilkinson P, Hansell DM, Janssens J, et al. Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph? Lancet 1995;345:1074-8. 12 Reid A, de Klerk N, Ambrosini G, et al. The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis. Occup Environ Med 2005;62:665-9. 1 lth European Forum on Quality Improvement in Health Care 26-28 April 2006, Prague, Czech Republic For further information please go to: wvAV.quality.bmjpg.com Book early to benefit from a discounted delegate rate www.occenvmed.com COMMENTARY Downloaded from oem.bmjjournals.com on 16 September 2005 663 Epidemiology Are lung and pleural benign asbestos induced diseases a preliminary step in the pathogenic process of mesothelioma and lung cancer development? M Goldberg Commentary on the paper by Reid et al (see page 665) sbestos is and will remain for cancer. If benign pleural and lung Adecades a major public health problem in many countries: it diseases are on the pathways towards cancer, an additional specific question is has been estimated that in Westewrhnether this is a necessary step, or if Europe alone, about 500 000 cancer benign pleural and lung diseases only deaths due to asbestos exposure will increase the risk of developing a cancer occur up to 2029.1 Apart from being of by interacting with other factors, such public health concern, there are some as tobacco smoke. major scientific questions about the Animal data give some indications health effects of asbestos exposure: that fibrosis of the mesothelial sera may What are the specific chemical and precede malignant mesothelioma devel morphological characteristics of asbes opment.4 Animal experimentation also tos fibres involved in carcinogenesis? Is showed that lung cancer develops more fibre persistency in the lung parench frequently among rats that developed yma an important determinant of the alveolar inflammation and fibrosis than risk of developing a malignant mesothe among those who did not.' However, lioma? Is the potency for lung cancer these studies in favour of a carcinogenic induction the same regardless the type mechanism involving inflammation and of asbestos fibres (chrysotile, amosite, fibrosis as a preliminary stage of cancer crocidolite, tremolite, anthophyllite)? Is had some limitations,' and do not lung or pleural fibrosis a preliminary provide sufficient support for the step in the process of mesothelioma and hypothesis of a single pathogenic pro lung cancer development? cess for benign and malignant asbestos Research done by pathologists, biolo induced disease. gists, and epidemiologists, provides Epidemiological studies considering findings that may be crucial to answer the association between asbestos expo these questions.2 It would be of utmost sure and cancer of the lung or malig importance to better understand the nant mesothelioma tested whether, relations between benign pleural dis when adjusting for asbestos exposure, eases (plaques and pleural calcification, the excess cancer risk disappeared for pleural thickening), pulmonary fibrosis those with no history of chest radio (asbestosis), and the risks of lung graphic abnormalities (single sequential cancer and malignant mesothelioma. pathogenic process hypothesis), or Most studies that looked at asbestos remained at the same level (common induced benign pleural and/or lung cause without interaction hypothesis), diseases among patients suffering from or was still raised but at a lower level cancer found that these diseases were (common cause with interaction also present.' hypothesis). Both benign and malignant diseases In cohort studies of asbestos workers, have been associated with asbestos where chest radiographs and estimates exposure. To understand the mechan of cumulative exposure were available, isms of asbestos induced cancers, we findings were not consistent: some should understand whether the strong found that, when adjusting for cumula association between benign and malig tive exposure to asbestos, the lung nant asbestos related diseases only cancer risk was not increased among reflects the common cause--asbestos-- those having pleural plaques or radi without being involved in the same ological symptoms of asbestosis com pathological process, or whether benign pared to those without radiological diseases are a preliminary step towards abnormalities, whereas some found such an increased risk.6 7 Contradictory results were also published about pleural plaques or asbestosis and malignant mesothelioma.8"11' In a casecontrol study of lung cancer of hospital patients, Wilkinson and colleagues" showed that the increase of the odds ratios associated with asbestos expo sure was of the same order among subjects with fibrosis radiographic symptoms and among subjects without abnormalities. In this context, the study of Reid et al, published in this issue,12 brings new important findings about the relations between exposure to crocidolite asbes tos, benign lung and pleural diseases, and the risk of malignant mesothe lioma. Unique features of this cohort study are the long follow up, the availability of good quantitative esti mates of asbestos exposure for every subject included in the cohort, as well as standardised chest radiographs. The investigators could thus show that for the same level of asbestos exposure, the risk of pleural mesothelioma was not different for subjects with and without radiological signs of lung and pleural fibrosis, whereas the risk of peritoneal mesothelioma was higher for those showing radiological signs. However, the risk of peritoneal mesothelioma associated with benign pleural diseases was lower when adjustments were made for asbestos exposure, indicating that there was some excess risk due to benign chest diseases. These results are in favour of the common cause without interaction hypothesis for pleural cancer, pleural abnormalities and asbestosis being proxies of asbestos exposure without bearing a specific contribution to the increase in the risk of mesothelioma. For peritoneal cancer, the findings give some strength to the common cause with interaction hypothesis. There are however several questions that remain open. First, the cohort was exposed to crocidolite asbestos, while other types of asbestos--especially less biopersisient forms--may act differently during the carcinogenic process. Another concern is exposure assessment: as the authors acknowledge, the higher exposures may have been underestimated. In such a case, as mesothelioma of the perito neum is associated with higher cumu lative exposure than pleural mesothelioma, even if benign chest diseases were not involved in the carci nogenic process, one would expect that some relation between radiographic abnormalities due to heavy asbestos exposure would still be apparent after adjusting for asbestos exposure. Thus, the findings from the study by Reid et al do not totally discard www.occenvmed.com