Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

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 investi...

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Main Authors: Cleo Robinson, Helman Alfonso, Samantha Woo, Amy Walsh, Nola Olsen, Arthur W Musk, Bruce W S Robinson, Anna K Nowak, Richard A Lake
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4122392?pdf=render
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spelling doaj-223d19bbba744fc59f8b523958d7b5562020-11-24T21:42:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10302510.1371/journal.pone.0103025Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.Cleo RobinsonHelman AlfonsoSamantha WooAmy WalshNola OlsenArthur W MuskBruce W S RobinsonAnna K NowakRichard A LakeMesothelioma 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.http://europepmc.org/articles/PMC4122392?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Cleo Robinson
Helman Alfonso
Samantha Woo
Amy Walsh
Nola Olsen
Arthur W Musk
Bruce W S Robinson
Anna K Nowak
Richard A Lake
spellingShingle Cleo Robinson
Helman Alfonso
Samantha Woo
Amy Walsh
Nola Olsen
Arthur W Musk
Bruce W S Robinson
Anna K Nowak
Richard A Lake
Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
PLoS ONE
author_facet Cleo Robinson
Helman Alfonso
Samantha Woo
Amy Walsh
Nola Olsen
Arthur W Musk
Bruce W S Robinson
Anna K Nowak
Richard A Lake
author_sort Cleo Robinson
title Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
title_short Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
title_full Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
title_fullStr Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
title_full_unstemmed Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
title_sort statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description 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.
url http://europepmc.org/articles/PMC4122392?pdf=render
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