Cancer’s Subtle Influence on Forensic DNA Age Estimation: New Insights from Zurich Researchers
In a groundbreaking study recently published in Aging-US, scientists from the University of Zurich have illuminated how cancer, a complex and multifaceted disease, interacts with forensic tools used to estimate human age from biological samples. These findings provide essential clarity on the robustness of DNA methylation-based age prediction methods, particularly when confronted with pathological distortions caused by cancer. The study addresses a critical question in forensic science: does the presence of cancer in an individual’s biological material compromise the accuracy of age estimation techniques that rely on epigenetic markers?
Forensic age estimation has leveraged the phenomenon of DNA methylation, a chemical modification of DNA molecules that accumulates predictably with age. This epigenetic clock functions by measuring methylation levels at specific CpG sites across the genome, which change due to developmental and aging processes. As age-related methylation changes are generally stable and reproducible, forensic experts use them to determine the age of individuals from trace biological evidence, such as blood found at crime scenes. However, cancer – with its dynamic epigenetic remodeling and aberrant cellular proliferation – poses a potential confounder, potentially skewing these methylation signatures and thus age predictions.
The research team, led by Charlotte Sutter and her colleagues at the Zurich Institute of Forensic Medicine and Onkozentrum Zurich, systematically assessed the impact of different cancer types on the accuracy of age estimation using the VISAGE enhanced age prediction tool. This widely adopted forensic methodology amalgamates methylation data from select CpG sites, providing a reliable estimate of chronological age. To explore cancer’s influence, the authors analyzed blood samples from a cohort of 100 cancer patients subdivided into solid tumor cases and hematologic malignancies, compared against 102 healthy control individuals.
Intriguingly, the study demonstrated that age estimates derived from the blood of individuals with solid tumors such as breast and lung cancers showed only marginal reductions in prediction precision compared to controls. The mean absolute error (MAE) in this group was approximately 4.66 years, which, while slightly elevated relative to healthy subjects, remains within a range acceptable for forensic applications. This suggests that the epigenetic aging clock measured by VISAGE remains relatively stable in the context of most solid cancers, despite the substantial metabolic and cellular deregulations induced by tumorigenesis.
Contrastingly, hematologic cancers painted a more complex picture. For patients suffering from blood cancers including chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), the researchers observed greater variability and occasionally striking deviations in age estimation. In a small subset of these cases, the predicted ages were overestimated by as much as 50 years, emphasizing how aggressive malignancies within the hematopoietic system might drastically distort DNA methylation patterns. These extreme outliers underscore the sensitive interplay between disease pathology and epigenetic biomarkers, signaling caution in forensic interpretations involving hematologic cancer samples.
Despite these select anomalies, the overall conclusion of the study underscores the resilience of epigenetic age estimation methodologies. Most cancer patients’ blood methylation patterns did not deviate substantially from those observed in healthy individuals. Neither the malignancy stage nor ongoing treatment regimens exhibited a consistent effect on age prediction accuracy. These outcomes affirm that, under typical forensic scenarios, cancer-induced epigenetic alterations seldom invalidate forensic age estimates.
The biological mechanisms underpinning these observations merit consideration. DNA methylation changes in cancer often reflect tumor-specific processes, including hypermethylation of tumor suppressor genes or global hypomethylation leading to genomic instability. However, these alterations may remain localized to tumor tissues, with peripheral blood methylation profiles primarily reflecting systemic aging rather than tumor epigenetics. This compartmentalization likely explains the preserved predictive fidelity of methylation-based age estimators applied to blood samples, except in aggressive hematologic cancers that directly originate in blood cells.
These findings bear significant implications for forensic science and criminal justice. Given the increasing reliance on molecular age predictors for investigations ranging from identifying unknown victims to clarifying suspect profiles, establishing the factors that can bias these tools is paramount. This study advises that forensic practitioners maintain awareness of the potential for severe deviations caused by rare, agitated blood cancers but that no urgent modifications to standard analysis protocols are currently necessary.
Moreover, this research contributes to a broader understanding of epigenetic variation in disease contexts. By demonstrating the differential impact of solid versus hematologic tumors on systemic methylation clocks, it encourages future investigations into how other pathological states might modulate forensic biomarkers. The intersection of medical epigenetics and forensic science promises to refine age estimation further and enhance its utility across diverse populations.
The Zurich team’s work also highlights the power of interdisciplinary collaboration, combining forensic expertise with oncology and epigenomics to tackle real-world challenges. As epigenetic technologies evolve, incorporating multi-omic data and advanced machine learning algorithms, forensic age prediction will become increasingly precise and robust, even amid biological complexities like cancer.
In summary, the study “The influence of cancer on a forensic age estimation tool” provides compelling evidence that while cancer, particularly aggressive hematologic forms, may occasionally perturb DNA methylation age predictors, the overall reliability of these forensic tools remains intact. This reassurance is crucial for the accurate application of forensic science in legal contexts, supporting confidence in DNA-based age estimation despite the presence of disease.
Subject of Research: People
Article Title: The influence of cancer on a forensic age estimation tool
News Publication Date: 17-Jul-2025
Web References:
Image Credits: Copyright © 2025 Sutter et al., distributed under Creative Commons Attribution License (CC BY 4.0).
Keywords: aging, forensic age estimation, DNA methylation, cancer, age prediction, epigenetics, hematologic malignancies, solid tumors, forensic science, VISAGE tool, chronic lymphocytic leukemia, acute myeloid leukemia
