Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia
Δημιουργός/Συγγραφέας:	[EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis Gavriil M. Rantakokko P. Ladoukakis E. Botsivali M. Kelly R.S. Bergdahl I.A. Kiviranta H. Vermeulen R.C.H. Spaeth F. Hebbels D.G.A.J. Kleinjans J.C.S. de Kok T.M.C.M. Palli D. Vineis P. [EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A. on behalf of the EnviroGenomarkers consortium
Εκδότης:	Elsevier Ltd
Ημερομηνία:	2019
Γλώσσα:	Αγγλικά
ISSN:	0160-4120
DOI:	10.1016/j.envint.2019.01.068
Άλλο:	PubMed ID: 30776747
Περίληψη:	Objectives: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma. Methods: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene. Results: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis. Conclusions: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.
Τίτλος πηγής δημοσίευσης:	Environment International
Τόμος/Κεφάλαιο:	126
Σελίδες:	24-36
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	B-cell lymphoma DNA methylation Environmental toxicology Hazard assessment Molecular epidemiology Persistent organic pollutants
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2019 The Authors
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	National Heart, Lung, and Blood Institute, NHLBI: K01HL146980; European Geosciences Union, EGU: grand 226756
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο