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

Our plain-English summary of Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans, by C. Robinson, H. Alfonso, S. Woo, et al (PloS One, 2014).

The study

• Authors: C. Robinson, H. Alfonso, S. Woo, A. Walsh, N. Olsen, A.W. Musk, B.W. Robinson, A.K. Nowak, R.A. Lake
• Journal: PloS One
• Published: 2014;9(8):e103025
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This study tested whether statins, which are cholesterol-lowering drugs, reduced mesothelioma after asbestos exposure in mice and in people. In the animal experiment, MexTAg 299h transgenic mice were injected in the abdomen with two 3 mg doses of crocidolite asbestos, one month apart. They were fed atorvastatin at 100, 200 or 400 mg/kg of feed, or a plain diet, starting two weeks before exposure. Atorvastatin did not change survival (p = 0.84), time to first signs of disease, or disease progression. The human part studied 1,738 former workers and residents of the Wittenoom crocidolite mine area in Western Australia who reported their current medicines on a questionnaire from 1990. By June 2012, 107 had developed mesothelioma. Among people taking statins alone, 8 of 154 developed mesothelioma (adjusted hazard ratio 1.01, 95% CI 0.44 to 2.29). For statins combined with anti-inflammatory drugs (NSAIDs or COX-2 inhibitors), the hazard ratio was 0.91 (0.50 to 1.66), which was not statistically significant. The authors concluded that statins did not alter mesothelioma incidence in exposed mice or humans. They noted that later, unrecorded statin use among non-users could have biased the human results.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment in transgenic mice, combined with an analysis of a human cohort using Cox regression
• Who was studied: Mice: MexTAg 299h transgenic mice, matched for age and gender (figure legend gives n = 20). Humans: 1,738 of 2,363 participants in the Wittenoom 'Vitamin A programme' (former workers and residents of Wittenoom, Western Australia) who gave information on medication use. The programme began accepting participants in July 1990, and participants were followed to 30 June 2012, for an average of 11.94 years.
• Exposure: Crocidolite asbestos in both mice and humans. Mice received two intraperitoneal doses of 3 mg of Wittenoom crocidolite, one month apart, plus atorvastatin in their feed at 100, 200 or 400 mg/kg. Humans had lived or worked at Wittenoom and reported current use of statins (simvastatin, atorvastatin, pravastatin, rosuvastatin or fluvastatin), alone or with NSAIDs or COX-2 inhibitors. Dose, frequency and duration of use were not recorded.
• Main results:
  • In mice, atorvastatin at any dose did not alter incidence of, or survival with, mesothelioma (p = 0.84).
  • In mice, time from asbestos exposure to first diagnosis, and disease progression after diagnosis, did not differ significantly between diet groups.
  • In the Wittenoom cohort, 107 people had been diagnosed with mesothelioma by June 2012.
  • Among people taking statins alone, 8 of 154 (5.2%) developed mesothelioma, compared with 51 of 798 (6.4%) taking neither drug. The adjusted hazard ratio was 1.01 (95% CI 0.44 to 2.29), p = 0.99.
  • Among people taking statins together with NSAIDs or COX-2 inhibitors, 21 of 400 developed mesothelioma. The adjusted hazard ratio was 0.91 (95% CI 0.50 to 1.66), p = 0.77.
  • When measured from the date of first asbestos exposure, the hazard ratio for statins alone was 0.81 (95% CI 0.35 to 1.83), p = 0.61. For statins plus NSAIDs or COX-2 inhibitors it was 0.67 (95% CI 0.37 to 1.22), p = 0.19. The authors described the combination result as lower but not statistically significant.
• The authors' conclusion: The authors concluded that statins do not alter the incidence of mesothelioma in asbestos-exposed mice or humans.
• Limitations the authors state:
  • Statin use was recorded only once, in 1990. Some people counted as non-users may have started statins later, which could cause misclassification bias. The authors wrote that this could feasibly affect the results significantly.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Discovery, Apoptosis, Latency, Disease Progression, Crocidolite, Wittenoom.

Related studies

• Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort — C. Robinson, H. Alfonso, et al. (2014)
• MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma — C. Robinson, A. Walsh, et al. (2011)
• High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients — L. Cantini, F. Pecci, et al. (2021)
• Re: Comments on 'High-intensity statins are associated with improved clinical activity of programmed cell death protein 1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients' — L. Cantini, F. Pecci, et al. (2021)
• Re: 'High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients' — A. Hara, M. Matsuda, et al. (2021)
• The antioxidants vitamins A and E and selenium do not reduce the incidence of asbestos-induced disease in a mouse model of mesothelioma — C. Robinson, S. Woo, et al. (2012)

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