In a recently published article, Guarrera and colleagues report differential DNA methylation between malignant pleural mesothelioma (MPM) patients and cancer-free controls. These data represent some of the first evidence of detectable differences in DNA methylation in asbestos-exposed individuals with and without MPM. For asbestos defendants, these results provide support for the potential use of DNA methylation profiles to distinguish between asbestos-exposed MPM cases from non-MPM cases and may improve MPM risk estimation in individuals with known exposure to asbestos.
DNA methylation is an epigenetic mechanism that regulates gene expression and cell differentiation. However, abnormal DNA methylation is linked to several adverse outcomes, including disease. Thus, DNA methylation can be used as a biomarker for the detection and diagnosis of disease (e.g., Alzheimer’s disease, cancer, schizophrenia, multiple sclerosis).
Briefly, Guarrera et al. measured DNA methylation levels in DNA from whole blood collected from 163 asbestos-exposed MPM patients and 137 asbestos-exposed cancer-free controls. Cumulative asbestos exposure was determined through questionnaires of occupational history, residential history, and lifestyle habits. Evidence of differential methylation was found between asbestos-exposed MPM patients and asbestos-exposed controls, primarily in immune system and/or inflammation-related genes.
More specifically, the authors report lower methylation rates of FOXK1, a gene previously implicated in tumor onset and progression in colorectal, esophageal, and gastric cancers to name a few. Moreover, FOXK1 directly interacts with the BAP1 tumor suppressor gene, whose role in mesothelioma is well-described by Carbone and others. Using FOXK1, the authors were able to distinguish between asbestos-exposed MPM cases from asbestos exposed non-MPM cases. Although it is not known if differential methylation rates reflect a causal factor underlying the development MPM or are the result of the disease itself, these data represent some of the first evidence of measurable changes in DNA related to MPM.
As alleged asbestos exposure dose continues to decline (e.g., occupational “take-home” exposure, outside ambient air), testing for genetic biomarkers of individual exposure and susceptibility is an increasingly important tool to prove or disprove causation in litigation. Novel biomarkers, such as the one described by Guarrera and colleagues, have the potential to not only distinguish asbestos-induced MPM from non-asbestos-induced MPM, but to identify individuals especially prone to developing MPM independent of asbestos exposure.
Citation: Guarrera S, Viberti C, Cugliari G, Allione A, Casalone E, Betti M…Matullo G. Peripheral blood DNA methylation as potential biomarker of malignant pleural mesothelioma in asbestos-exposed subjects. J Thorac Oncol. 2018 Nov 5. pii: S1556-0864(18)33412-9.
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