TY - JOUR
T1 - Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma
T2 - The EPIC prospective cohort
AU - Allione, Alessandra
AU - Viberti, Clara
AU - Cotellessa, Ilaria
AU - Catalano, Chiara
AU - Casalone, Elisabetta
AU - Cugliari, Giovanni
AU - Russo, Alessia
AU - Guarrera, Simonetta
AU - Mirabelli, Dario
AU - Sacerdote, Carlotta
AU - Gentile, Marco
AU - Eichelmann, Fabian
AU - Schulze, Matthias B.
AU - Harlid, Sophia
AU - Eriksen, Anne Kirstine
AU - Tjønneland, Anne
AU - Andersson, Martin
AU - Dollé, Martijn E.T.
AU - Van Puyvelde, Heleen
AU - Weiderpass, Elisabete
AU - Rodriguez-Barranco, Miguel
AU - Agudo, Antonio
AU - Heath, Alicia K.
AU - Chirlaque, María Dolores
AU - Truong, Thérèse
AU - Dragic, Dzevka
AU - Severi, Gianluca
AU - Sieri, Sabina
AU - Sandanger, Torkjel M.
AU - Ardanaz, Eva
AU - Vineis, Paolo
AU - Matullo, Giuseppe
N1 - Publisher Copyright:
© 2022 UICC.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - 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.
AB - 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.
KW - DNA methylation
KW - cancer biomarkers
KW - mesothelioma
KW - prospective nested case-control study
UR - http://www.scopus.com/inward/record.url?scp=85141481237&partnerID=8YFLogxK
U2 - 10.1002/ijc.34339
DO - 10.1002/ijc.34339
M3 - Article
C2 - 36305648
AN - SCOPUS:85141481237
SN - 0020-7136
VL - 152
SP - 725
EP - 737
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -