UW Professor Co-Writes Study That Could Lead to Better Early-Stage Cancer Detection

A new study -- co-written by Konstantinos Mamis, an assistant professor of mathematics at the University of Wyoming -- reveals a surprising mechanism behind one of the most promising tools in cancer detection: cell-free DNA (cfDNA) in blood.

The study, titled “Early-stage cancer results in a multiplicative increase in cell-free DNA originating from healthy tissue,” appeared June 3 in Journal of the Royal Society Interface. The journal publishes cross-disciplinary research at the interface between the physical and life sciences.

Ivana Bozic, an associate professor in the Department of Applied Mathematics at the University of Washington and an affiliate faculty member in the Herbold Computational Biology Program at the Fred Hutchinson Cancer Center, was the paper’s other co-writer.

In this study, Mamis and Bozic combine mathematical modeling with data analysis of large, previously published clinical data sets to provide new insight into how early-stage cancer affects the body.

“Cell-free DNA -- small fragments of DNA circulating in the bloodstream -- is increasingly used in ‘liquid biopsies’ to detect cancer without invasive procedures,” Mamis says. “However, understanding where this DNA comes from and how it changes in early-stage disease has remained a major challenge.”

Mamis and Bozic analyzed data across multiple cancer types and found that, even in early-stage cancer, the ways that cfDNA levels increase are both multiplicative and specific to the type of cancer, ranging from about 1.3-fold in lung cancer to over 10-fold in liver cancer.

Crucially, the study shows that this increase does not primarily come from the tumor itself but, instead, from healthy tissue throughout the body. To explain this unexpected finding, the researchers developed a mathematical model of cfDNA dynamics. Their analysis suggests that the presence of cancer leads to increased DNA shedding from healthy tissue, which is then further amplified because the body’s DNA-clearing system becomes overwhelmed, resulting in disproportionately higher levels of cfDNA in the body.

This insight has important implications for early cancer detection.

“Our work shows that even small, early-stage cancers can leave a strong, systemwide signal in the bloodstream -- not by shedding large amounts of DNA directly from the tumor, but by affecting how the body releases and clears DNA overall,” Mamis says.

In several cancer types, cfDNA levels alone were shown to provide high diagnostic accuracy, highlighting their potential for simple and cost-effective screening tools. 

More broadly, the work provides a quantitative framework for interpreting cfDNA measurements and offers a new perspective on how early-stage tumors affect the whole body. This could help improve the design and interpretation of next-generation liquid biopsy tests.