Early-stage cancer results in a multiplicative increase in cell-free DNA originating from healthy tissue

Abstract

AbstractSources of elevated cell-free DNA (cfDNA) in early-stage cancer patients are poorly understood. Leveraging a rich dataset of cfDNA in healthy individuals and cancer patients, we find that a large majority of cfDNA in cancer patients originates from non-tumor sources, and that the presence of early-stage cancer results in a multiplicative increase in the concentration of cfDNA originating from healthy tissue. The magnitude of the multiplicative increase is cancer-type specific and ranges from a ∼1.3-fold increase in lung cancer, to a ∼12-fold increase in patients with liver cancer. As cfDNA is cleared in the liver, the large increase in patients with liver cancer may imply that the systemic increase in cfDNA levels in the presence of cancer is due to slower clearance rate rather than higher cell turnover.