EPIC Working Groups - Cancer Working Groups

The Mesothelioma Working Group

Malignant pleural mesothelioma (MPM) is a rare aggressive tumour whose main risk factor is asbestos exposure. Starting in the nineties, asbestos use was banned in several countries. However, potential sources of asbestos exposure are still widespread: several sites where asbestos was mined or manufactured in the past and millions of square meters of asbestos cement slates still need to be cleared, creating a risk environment for nearby dwellers. In Italy, for example, over 30.000 such sites are reported. MPM mortality rate is expected to increase by 5–10% per year in most industrialized countries for the next 2 decades, despite asbestos abatement efforts.

MPM has poor prognosis and is likely due to the lack of an efficient screening approach for its early detection, and to the ineffectiveness of current treatments. Currently, no sensitive screening method is available to monitor asbestos-exposed subjects, who have high risk of developing MPM. In recent years, epigenetic markers, such as DNA methylation (DNAm) and microRNAs (miRNAs) profiles, are gaining popularity as possible early diagnosis and prognostic biomarkers in cancer research. The major goal of the EPIC Mesothelioma Working Group is to improve early detection and screening, in particular by evaluating risk prediction models and by identifying pre-diagnostic biomarkers.

Current project involves the investigation of epigenetic and proteomic changes in blood and serum samples related to MPM risk and to assess the effects of asbestos exposure.

Since only a small portion of asbestos exposed people develop MPM, the WG also focuses on the study of germline mutations that can increase MPM susceptibility in asbestos exposed subjects.

Genomic (SNP arrays and NGS analysis), epigenomic (DNA methylation and miRNA) and biochemical (proteomics in serum) data will be integrated with the final goal to provide tools to detect early effects, in order to possibly allow also a more effective therapeutic intervention.

Selected publications

  1. Allione et al., Proteomics in the mesothelioma EPIC cohort (in preparation)

  2. Casalone E et al. Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study. Cancers (Basel). 2022 Dec 25;15(1):125. doi: 10.3390/cancers15010125. PMID: 36612122

  3. Allione A et al. Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort. Int J Cancer 2023 Feb 15;152(4):725-737. doi: 10.1002/ijc.34339. Epub 2022 Nov 5. PMID: 36305648

  4. Cugliari G, et al. DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma. Cancers (Basel). 2020 Nov 21;12(11):3470. doi: 10.3390/cancers12113470. PMID: 33233407; PMCID: PMC7700347.

  5. Cugliari G, et al. New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment. Cancers (Basel). 2021 May 27;13(11):2636. doi: 10.3390/cancers13112636. PMID: 34071989; PMCID: PMC8199167.

  6. Guarrera S et al., Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects. J Thorac Oncol. 2019 Mar;14(3):527-539. doi: 10.1016/j.jtho.2018.10.163. PMID: 30408567

  7. Betti M et al., Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes. Genes Chromosomes Cancer. 2018 Nov;57(11):573-583. doi: 10.1002/gcc.22670. PMID: 30338612

  8. Casalone E et al., DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response. Arch Toxicol. 2018 May;92(5):1785-1795. doi: 10.1007/s00204-018-2179-y. Epub 2018 Mar 9. PMID: 29523930

  9. Kharazmi E et al, Familial risk of pleural mesothelioma increased drastically in certain occupations: A nationwide prospective cohort study. Eur J Cancer. 2018 Nov;103:1-6. doi: 10.1016/j.ejca.2018.07.139. Epub 2018 Sep 6. PMID: 30196105

  10. Plato N et al., Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban. Epidemiol Health. 2016 Sep 20;38:e2016039. doi: 10.4178/epih.e2016039. eCollection 2016. PMID: 27866405

  11. Tunesi S et al., Gene-asbestos interaction in malignant pleural mesothelioma susceptibility. Carcinogenesis. 2015 Oct;36(10):1129-35. doi: 10.1093/carcin/bgv097. Epub 2015 Jul 2. PubMed PMID: 26139392

  12. Matullo G et al., Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study. PLoS One. 2013 Apr 23;8(4):e61253. doi: 10.1371/journal.pone.0061253. Print 2013. PubMed PMID: 23626673

  13. Agudo A et al, Occupation and risk of malignant pleural mesothelioma: A case-control study in Spain. Am J Ind Med. 2000 Feb;37(2):159-68. doi: 10.1002/(sici)1097-0274(200002)37:2. PMID: 10615096

Contact details/Working Group leader

Prof. Giuseppe Matullo, PhD
Dept of Medical Sciences
University of Turin
Via Santena 19, Turin, Italy