Blood Proteins Reveal Signals Linked to Prostate Cancer Risk Years Before Diagnosis

Prostate cancer is the most commonly diagnosed cancer in men worldwide. While many tumors grow slowly, aggressive forms can be life-threatening, underscoring the need for earlier risk identification. Established risk factors such as age and genetics are largely unmodifiable, but biological markers could refine risk assessment. New findings suggest that blood proteins measured years before diagnosis may reveal signals linked to future prostate cancer risk, including aggressive disease.

Oxford Population Health researchers led a large population-based study using blood protein profiling to examine future prostate cancer risk. The approach measured more than 6,000 circulating proteins in stored blood samples. The proteins were linked to biological processes including immune activity, cell adhesion, blood vessel formation, and genes already known to be important in prostate cancer.

The study analyzed blood samples from 982 men who later developed prostate cancer and a randomly selected sample of 1,573 men from the European Prospective Investigation into Cancer and Nutrition. Participants were followed for around 16 years. The researchers looked for protein differences associated with later prostate cancer diagnosis, with particular attention to aggressive disease.

Twelve proteins were associated with prostate cancer diagnosed more than 15 years after blood collection. These included GZMK, a protein produced by immune cells involved in recognizing and destroying abnormal cells. Seven proteins were linked to aggressive prostate cancer, and ANKRD1 was consistently associated with several serious forms of disease, including cancers that had spread or were ultimately fatal.

The study also found associations with blood levels of proteins produced by genes already known to be important in prostate cancer, including ERBB3, KRAS, and NRAS. These proteins were particularly linked to aggressive prostate cancer diagnosed around a decade later. The findings were published in European Urology on October 21, 2026, and presented at the American Society of Human Genetics (ASHG) Annual Meeting.

The researchers compared their results with other large population studies and genetic evidence to test the robustness of the findings. Several associations were supported by these additional analyses, although not all could be confirmed. The proteins are not yet suitable for clinical testing, and future work through the Prostate Cancer Aetiology and Prevention Programme will investigate whether they could contribute to better prediction or prevention strategies.

“Prostate cancer is not one disease. Many prostate cancers grow slowly and may never cause harm, while others are aggressive and can be life-threatening. By measuring thousands of proteins in blood collected years before diagnosis, we can begin to investigate how men who later develop aggressive prostate cancer may differ from men who do not. Ultimately, we hope this will help us understand the biology of aggressive prostate cancer and identify markers that could improve how we assess risk in the future,” said Dr. Zhe Huang, first author of the study and a postdoctoral epidemiologist at Oxford Population Health.

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