Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer
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Danielle Fernandes Durso1,2,*, Maria Giulia Bacalini3,*, Claudia Sala4,9, Chiara Pirazzini3, Elena Marasco1, Massimiliano Bonafé1, Ítalo Faria do Valle4, Davide Gentilini5, Gastone Castellani4,9, Ana Maria Caetano Faria6, Claudio Franceschi3,*, Paolo Garagnani1,7,8,9,*, Christine Nardini10,11,*
1Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy
2National Counsel of Technological and Scientific Development (CNPq), Ministry of Science Technology and Innovation (MCTI), Brasilia, Brazil
3IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
4Department of Physics and Astronomy, University of Bologna, Bologna, Italy
5Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan, Italy
6Biochemistry and Immunology Department, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil
7Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna, Italy
8Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy
9Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
10Personal Genomics S.r.l., Verona, Italy
11CNR IAC “Mauro Picone”, Rome, Italy
*These authors contributed equally to this work
Christine Nardini, email: [email protected]
Paolo Garagnani, email: [email protected]
Claudio Franceschi, email: [email protected]
Keywords: epigenetic clock, ELOVL2, FHL2, cancer, blood
Received: October 19, 2016 Accepted: February 12, 2017 Published: February 21, 2017
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-of-the-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.
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