135 Chrysotile asbestos accelerates tumour development in mouse models of mesothelioma and lung cancer

Abstract Background Inhalation of asbestos is the primary cause of Pleural Mesothelioma and is an acknowledged risk factor for all types of Lung Cancer. Persistence of asbestos fibres in the lungs and pleural cavity drives chronic inflammation, leading to the accumulation of driver mutations in exposed tissues and the eventual emergence of invasive malignant disease. Chronic inflammation additionally drives local immune suppression, likely contributing to poor responses to immunotherapy. The risk of Lung Cancer and Mesothelioma varies by type of asbestos, with Amphiboles (eg Amosite, Crocidolite) linked to greater risk of Mesothelioma than Serpentine (ie Chrysotile), whereas Chrysotile links to greater risk of Lung Cancer than Amphiboles. The vast majority of Asbestos imported into the UK since 1950 was Chrysotile, however, the contribution of asbestos to Lung Cancer in the UK has not been directly investigated. Methods We analysed data from Public Health Scotland (years 1998 to 2022) to determine if the geographic distribution of Lung Cancer incidence across Scotland is related to that of Mesothelioma, and used dose-controlled intrapleural or intratracheal delivery of asbestos fibres into genetically susceptible mice to determine the impact of defined asbestos exposures on Mesothelioma and Lung tumour development, respectively. Results Across the 17 Scottish Health Boards, standardised incidence rates for these cancers, averaged over 1998 to 2022, were directly correlated, with a Pearson Coefficient R = 0.848. By comparison, Mesothelioma showed no correlation with Pancreatic or Prostate Cancer incidence. Intrapleural injection of 25 ug Chrysotile or Amosite fibres resulted in similarly accelerated onset of morbidity in a genetically predisposed mouse model of Mesothelioma. Repeated oral delivery (5 × 10 ug) of Chrysotile fibres additionally accelerated tumour initiation and onset of morbidity in a mouse model of KRas-driven Lung Adenocarcinoma. Conclusions We conclude from these analyses that the contribution of asbestos to Lung Cancer in Scotland may be greatly underestimated.