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Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort |
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| Authors: | Alessandra Allione Clara Viberti Ilaria Cotellessa Chiara Catalano Elisabetta Casalone Giovanni Cugliari Alessia Russo Simonetta Guarrera Dario Mirabelli Carlotta Sacerdote Marco Gentile Fabian Eichelmann Matthias B Schulze Sophia Harlid Anne Kirstine Eriksen Anne Tjønneland Martin Andersson Martijn ET Dollé Heleen Van Puyvelde Elisabete Weiderpass Miguel Rodriguez-Barranco Antonio Agudo Alicia K Heath María-Dolores Chirlaque Thérèse Truong Dzevka Dragic Gianluca Severi Sabina Sieri Torkjel M Sandanger Eva Ardanaz Paolo Vineis Giuseppe Matullo |
| Affiliation: | 1. Department of Medical Sciences, University of Turin, Turin, Italy;2. IIGM—Italian Institute for Genomic Medicine, c/o IRCCS, Turin, Italy;3. Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates “G. Scansetti”, University of Turin, Turin, Italy;4. Unit of Cancer Epidemiology, Città Della Salute e Della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy;5. A.O.U. Federico II, Naples, Italy;6. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany German Center for Diabetes Research (DZD), Neuherberg, Germany;7. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany;8. Department of Radiation Sciences, Umeå University, Umeå, Sweden;9. Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark;10. Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark Department of Public Health, University of Copenhagen, Copenhagen, Denmark;11. Department of Public Health and Clinical Medicine, Sustainable Health, Umeå University, Umeå, Sweden;12. Centre for Health Protection National Institute for Public Health and the Environment, Bilthoven, The Netherlands;13. International Agency for Research on Cancer, World Health Organisation, Lyon, France;14. Escuela Andaluza de Salud Pública (EASP), Granada, Spain Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain;15. Unit of Nutrition and Cancer, Catalan Institute of Oncology—ICO, L'Hospitalet de Llobregat, Barcelona, Spain Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain;16. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK;17. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain;18. Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome, Heredity, Cancer and Health” Team, Paris, France;19. Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome, Heredity, Cancer and Health” Team, Paris, France Centre de Recherche sur le Cancer de l'Université Laval, Département de Médecine Sociale et Préventive, Faculté de Médecine, Québec, Canada Axe Oncologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Canada;20. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Via Venezian, Milan, Italy;21. Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway;22. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain Navarra Public Health Institute, Pamplona, Spain IdiSNA, Navarra Institute for Health Research, Pamplona, Spain;23. MRC Centre for Environment and Health, Imperial College London, London, UK |
| Abstract: | Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification. |
| Keywords: | cancer biomarkers DNA methylation mesothelioma prospective nested case-control study |
