title: 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.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma.
  
  
  METHODS
  A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site).
  
  
  RESULTS
  Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively.
  
  
  CONCLUSIONS
  We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.
authors.affiliation: National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia. Electronic address: cleo.robinson@uwa.edu.au.
authors.forename: Cleo
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway Crawley, WA 6009, Australia.
authors.forename: Helman
authors.initials: H
authors.lastname: Alfonso
authors.affiliation: National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Woo
authors.affiliation: Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway Crawley, WA 6009, Australia.
authors.forename: Nola
authors.initials: N
authors.lastname: Olsen
authors.affiliation: Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway Crawley, WA 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia 6009, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Bill Musk
authors.affiliation: National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia.
authors.forename: Bruce W S
authors.initials: BW
authors.lastname: Robinson
authors.affiliation: National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
mesh_terms: D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001194:Asbestos / Q000009:adverse effects*; D001241:Aspirin / Q000627:therapeutic use; D018890:Chemoprevention; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control; D000086002:Mesothelioma, Malignant; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D014904:Western Australia / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D001194:Asbestos; D001241:Aspirin
keywords: Asbestos-induced mesothelioma; COX-2 Inhibitors; Cancer prevention; Mouse model; Non-steroidal anti-inflammatory drugs; Patient cohort