Abstract
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.
Highlights
Cancer is an age related disease [1,2,3,4,5]
We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development
To confirm an expand these promising findings we explored the reproducibility of this observation in an independent cohort collected by the Human Genetics Foundation (HuGeF, Turin, Italy) including prospective breast cancer and colorectal cancer (CRC) data [44]
Summary
Cancer is an age related disease [1,2,3,4,5]. exploration of the association between markers of ageing and cancer represents an obvious step to bring advances in both research areas.Biomarkers that linearly change with chronological age are available to the scientific community and span from anatomical (e.g. ocular biomarkers [6]) to molecular ones including micro-RNAs levels [7, 8], protein modifications [9] and telomeres’ length [10].DNA methylation-based biomarkers have gained relevance in the last few years for many reasons. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development.
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