Understanding the genetics of malignant mesothelioma susceptibility and prognosis

Creaney J, Hui J, Robinson BWS, Brims F.


Synopsis (lay): Mesothelioma is an incurable and aggressive tumour of the membrane that lines the chest and abdominal cavities and cover the lungs and bowel caused almost exclusively by asbestos exposure. We aim to identify changes that occur in DNA following asbestos-exposure, and explore whether these changes are associated with the increased chance of later developing this cancer. In the long term targeting these changes may reduce the risk of asbestos-exposed people developing mesothelioma.

Synopsis (scientific): Mesothelioma is an incurable and aggressive tumour with increasing incidence worldwide. Median survival is less than 12 months and the disease is uniformly fatal. The principle etiological agent of mesothelioma is asbestos, but the underlying biological processes involved in disease pathogenesis following exposure to this naturally occurring mineral are poorly understood. A growing body of data is clearly pointing to the causal involvement of epigenetic changes in a variety of complex human diseases and conditions. These epigenetic changes can be induced by environmental factors, such as diet, stress and smoking. The effect of asbestos exposure on the global pattern of DNA methylation and potential involvement in mesothelioma has not been explored. We now aim to perform epigenetic studies in our cohort of well characterised asbestos-exposed but healthy ‘control’ individuals and mesothelioma cases. Initially the cohort was established to study people exposed to asbestos through the Wittenoom mining operations; for some participants over 20 years of clinical data as well as biospecimens have been collected. Using, current state-of-the art genomic methodologies we will perform an epigenome wide association study and a longitudinal analysis of DNA methylation, followed by validation in an independent cohort from Italy. Not only could the results of this study identify new biomarkers of mesothelioma risk, but also, identify therapeutic targets that could be reset to the ‘normal’ state with specific inhibitors.

NCARD Research Team