TY - JOUR
T1 - Acceleration of leukocytes' epigenetic age as an early tumorand sex-specific marker of breast and colorectal cancer
AU - Durso, Danielle Fernandes
AU - Bacalini, Maria Giulia
AU - Sala, Claudia
AU - Pirazzini, Chiara
AU - Marasco, Elena
AU - Bonafé, Massimiliano
AU - do Valle, Ítalo Faria
AU - Gentilini, Davide
AU - Castellani, Gastone
AU - Faria, Ana Maria Caetano
AU - Franceschi, Claudio
AU - Garagnani, Paolo
AU - Nardini, Christine
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-ofthe- art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.
AB - Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-ofthe- art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.
KW - Cancer, blood
KW - ELOVL2
KW - Epigenetic clock
KW - FHL2
UR - http://www.scopus.com/inward/record.url?scp=85017017223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017017223&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.15573
DO - 10.18632/oncotarget.15573
M3 - Article
AN - SCOPUS:85017017223
VL - 8
SP - 23237
EP - 23245
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 14
ER -