The ticking time-bomb of asbestos: Its insidious role in the development of malignant mesothelioma

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Abstract

The relationship between asbestos exposure and malignant mesothelioma (MM) has been well established. Despite bans on asbestos use in an increasing number of nations, the prolonged latency from exposure to diagnosis, and the ongoing presence and use of these dangerous fibres, have led to the increasing prevalence of this deadly disease worldwide. Whilst occupational contact has been implicated in the bulk of diagnosed cases over the past 50 years, a significant proportion of disease has been linked to para-occupational, domestic and environmental exposure. In this review, we will provide an update on the impact of historical and ongoing asbestos contact in both occupational and non-occupational settings. Furthermore, we will address the unresolved controversies surrounding the use of chrysotile asbestos, the effect of gender and genetics on development of this disease, childhood mesothelioma and co-aetiological factors including SV40 exposure.

Section snippets

History of asbestos and its link to malignant mesothelioma (MM)

Asbestos, derived from the ancient Greek term for inextinguishable, is a collection of naturally occurring crystalline hydrated silicates existing within a fibrous form. Asbestos fibres are traditionally divided into serpentine and amphibole forms. Amphibole fibres are typically short, straight, stiff and associated with increased stability. They include amosite, crocidolite, anthophyllite, tremolite and actinolite, and have been primarily used for asbestos cement and tiles. Chrysotile is the

Occupational exposure

Occupational exposure to asbestos has long been identified as the principal risk factor for the development of MM, with asbestos mentioned in 30% of occupational-related cancer registrations and up to 50% of deaths, in a 2010 review of British workers from a variety of industries [16].

A cohort of 141 MM patients diagnosed between 1970 and 1979, reported 82% of men had occupational asbestos exposure (17% in women). This correlated with a median lung fibre concentration of 2.4 million/g tissue in

Para-occupational and domestic exposure

The identification of significant numbers of patients without any occupational asbestos exposure led to the recognition of para-occupational and domestic asbestos exposures, as risk factors for MM.

A multitude of studies have demonstrated the risks associated with living with people working in asbestos-related industries; with a doubling of lifetime risk in otherwise unexposed men and women living with an asbestos worker before the age of 30 [6]. Domestic exposure to work clothes soiled with

Environmental exposure

Exposure to naturally occurring asbestos, accounts for a significant proportion of MM cases in a number of global regions.

The presence and impact of large amounts of serpentine and ultramafic rocks in the Sierra Nevada, Coast ranges and Klamath mountains has been implicated as a cause for MM in Californian residents. In a case–control study of 6000 patients, those with a low probability workplace contact demonstrated an elevated odds ratio for MM compared to controls (OR 1.71 (1.32–2.21), cf.

The chrysotile controversy

Chrysotile comprises 95% of all asbestos utilised in the twentieth century and virtually all asbestos mined and in circulation worldwide today [66]. Much of the controversy surrounding ongoing asbestos mining and usage has centred on what is perceived as the low potential of this fibre to elicit MM. Numerous studies have been accused of displaying bias, and due to the profound socioeconomic consequences of its use, discussion has extended far beyond a simple matter of carcinogenicity.

Debate

Gender

Due to the over-representation of males in the high-risk occupations associated with asbestos exposure, it is not surprising that male gender is associated with the majority of MM diagnoses. Two separate Japanese studies demonstrated a predominance of males (87% for pleural MM and 69% for peritoneal cases) [97] [18]. A review of the SEER database suggests a higher rate of peritoneal mesothelial tumours in women (37% in females versus 13% in males) [98]. Whether this is a correct observation or

An ongoing concern

Despite established bans in 52 countries, over two million metric tons of asbestos remain in use worldwide. Ninety five percent is produced in Russia, China, Canada, Brazil, Kazakhstan and Zimbabwe [129], with more than 85% used to manufacture products in Asia and Eastern Europe. Approximately 125 million people remain exposed to asbestos globally within their place of work [130], often in countries that do not have strictly regulated workplace safety controls and where there are limited data

Conflict of interest

None to declare.

Reviewers

Jan van Meerbeeck, MD, PhD, Ghent University Hospital, Thoracic Oncology, De Pintelaan 185, B-9000 Gent, Belgium.

David Pfister, MD, Memorial Sloan-Kettering Cancer Center, Divison of Solid Tumor Oncology, 1275 York Avenue, NY 10021-6007, United States.

Funding

This work is supported by the Asbestos Disease Research Foundation. A. Linton is supported by the Signorelli Foundation. J. Vardy is supported by Cancer Institute NSW.

Anthony Linton is a medical oncologist and PhD candidate at the University of Sydney, investigating predictive and prognostic markers in malignant mesothelioma. He is the first recipient of the Biaggio Signorelli Fellowship, and has interests in translational research, mesothelioma, lung and gastrointestinal malignancies.

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  • Cited by (0)

    Anthony Linton is a medical oncologist and PhD candidate at the University of Sydney, investigating predictive and prognostic markers in malignant mesothelioma. He is the first recipient of the Biaggio Signorelli Fellowship, and has interests in translational research, mesothelioma, lung and gastrointestinal malignancies.

    Janette Vardy obtained her MD at the University of Newcastle, Australia and her medical oncology specialisation at the Sydney Cancer Centre. She completed a fellowship and PhD at Princess Margaret Hospital, Toronto, by investigating the effects of chemotherapy on cognitive function and fatigue. She holds a clinician-scientist position at the Sydney Cancer Centre, funded by the Cancer Institute, NSW.

    Stephen Clarke is a medical oncologist and clinical pharmacologist and is currently a professor of medicine at the Sydney Medical School. He obtained his medical degree from Sydney University in 1983 and then undertook specialty training in medical oncology. He completed a PhD at the Royal Marsden Cancer Hospital and the Institute of Cancer Research in Sutton, Surrey, UK. He is a senior staff specialist at Royal North Shore Hospital. He has clinical and translational research interests in mesothelioma, lung and colorectal cancer.

    Nico van Zandwijk obtained his medical degree at the University of Amsterdam, The Netherlands, and completed a PhD on pulmonary injury elicited by blood. He has served as secretary and chair of the European Organisation for Research and Treatment of Cancer (EORTC) Lung Cancer Group, he was a board director of the International Association for the Study of Lung Cancer (IASLC) and co-chaired the 14th World Conference on Lung Cancer in 2011. He has authored or co-authored over 210 peer-reviewed international papers and chapters. He is the current director of the Asbestos Diseases Research Institute, NSW, Australia and a professor at the Sydney Medical School.

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