Blood Proteins Hint at Prostate Cancer Risk Over a Decade Before Diagnosis

Blood drawn from healthy men, then stored for years, has now yielded a set of clues about who went on to develop prostate cancer. A team at Oxford Population Health analyzed those samples and reported that proteins tied to the immune system, cell adhesion, blood vessel formation and known prostate cancer genes were associated with a man's later risk of the disease, including its aggressive forms.

The work was published in European Urology and presented at the American Society of Human Genetics Annual Meeting. The researchers describe it as the largest population-based investigation to date of blood proteins and future prostate cancer risk, with particular attention to aggressive disease.

The backdrop is a gap in knowledge. Prostate cancer is the most commonly diagnosed cancer in men worldwide, yet little is understood about why some men develop it or why some tumors turn aggressive. The best-established risk factors, age and genetics, cannot be changed.

The team drew on the European Prospective Investigation into Cancer and Nutrition (EPIC). They studied blood samples from 982 men who later developed prostate cancer, alongside a randomly selected group of 1,573 men from the same cohort. More than 6,000 proteins were measured in each sample, and participants were followed for around 16 years.

Twelve proteins were linked to cancer diagnosed more than 15 years after the blood was collected. One was GZMK, produced by immune cells that recognize and destroy abnormal cells. That suggests, the researchers say, that immune processes may help hold prostate cancer in check long before diagnosis. Seven further proteins were tied to aggressive disease. One of them, ANKRD1, was consistently associated with several serious forms, including cancers that had spread or ultimately proved fatal. Other findings pointed to how cancer cells interact with surrounding tissue and how new blood vessels form.

The study also found links with blood levels of proteins made by genes already known to matter in prostate cancer: ERBB3, KRAS and NRAS. These were particularly associated with aggressive cancer diagnosed about a decade later. The authors stress that this does not mean cancer was already present when the blood was taken. Rather, the proteins may point to biological changes that accompany future disease. Senior author Karl Smith-Byrne, a professor, said such links offer new insight into the earliest stages and, alongside genetic evidence, could help identify pathways to target in preventing aggressive prostate cancer.

The limits are plainly stated. The team compared results with other large population studies and genetic evidence. Several findings held up, but not all could be confirmed. Most associations were modest, and the proteins are not yet suitable as clinical tests. More studies are needed to learn whether they could improve prediction of clinically significant prostate cancer.

First author Dr. Zhe Huang noted that prostate cancer is not one disease: many cases grow slowly and may never cause harm, while others are life-threatening. Dr. Iain Foulkes of Cancer Research UK called the results important new clues and a window into the disease's biology, including a possible immune role. Next, the Prostate Cancer Etiology and Prevention Program (PCAP), whose leads include Professor Ruth Travis, will test whether the findings can contribute to predicting or preventing the disease.