Pre-diagnosis plasma cell-free DNA reveals early signatures of prostate and breast cancer risk up to eight years prior to clinical detection.

Authors

Nicholas Cheng, Tom W Ouellette, Kimberly Skead, Althaf Singhawansa, Mitchell Elliott, David W Cescon, Scott V Bratman, Daniel D De Carvalho, David Soave, Philip Awadalla

Published in

Cell genomics. Pages 101364. Sep 21, 2026. Epub Sep 21, 2026.

Abstract

Genome-wide cell-free DNA (cfDNA) methylation profiling of 491 pre-diagnosis breast and prostate cancer plasma samples, some collected up to nine years before diagnosis, identifies early cancer-associated epigenetic alterations and predictive signatures. Differentially methylated regions were enriched in regulatory and repetitive elements and reflected cancer-tissue- and immune-cell-associated DNA methylation patterns. Logistic regression models trained on discovery set samples showed that cfDNA silencer-region methylation robustly predicted future prostate cancer, with high-risk individuals exhibiting a 3.55-fold increased hazard of developing prostate cancer. Enhancer hypermethylation modestly predicted incident breast cancer but strongly distinguished established late-stage breast cancers, with high-risk individuals showing a 2.3-fold increased hazard. These results highlight cfDNA methylation as a promising biomarker for early cancer risk prediction and surveillance.

PMID:
42767223
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

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