title: Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
abstract: Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia; Anatomical Pathology, PathWest, Perth, Western Australia, Australia.
authors.forename: Cleo
authors.initials: C
authors.lastname: Robinson
authors.affiliation: School of Public Health, Curtin University, Perth, Western Australia, Australia.
authors.forename: Helman
authors.initials: H
authors.lastname: Alfonso
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Woo
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Walsh
authors.affiliation: Occupational Respiratory Epidemiology, School of Population Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Nola
authors.initials: N
authors.lastname: Olsen
authors.affiliation: Occupational Respiratory Epidemiology, School of Population Health, University of Western Australia, Perth, Western Australia, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Musk
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia.
authors.forename: Bruce W S
authors.initials: BW
authors.lastname: Robinson
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, Western Australia, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001194:Asbestos / Q000009:adverse effects*; D000069059:Atorvastatin; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008654:Mesothelioma / Q000453:epidemiology* / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D001194:Asbestos; D000069059:Atorvastatin
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