Blood Proteins Predict Prostate Cancer Risk Years Before Diagnosis

A study led by researchers at Oxford Population Health has linked specific blood proteins—tied to the immune system, cell adhesion, blood vessel formation and known prostate cancer genes—to a man’s future risk of developing prostate cancer, including aggressive forms of the disease. The findings, published in European Urology, point to biological differences between men who went on to develop prostate cancer and those who didn’t, information that could eventually help identify men at higher risk.

Prostate cancer is the most commonly diagnosed cancer in men worldwide, yet it’s still unclear why some men develop it or why some tumors turn aggressive, and most known risk factors, like age and genetics, can’t be changed. The researchers analyzed blood samples from 982 men who later developed prostate cancer and 1,573 randomly selected men from the European Prospective Investigation into Cancer and Nutrition, measuring more than 6,000 proteins over roughly 16 years of follow-up—the largest population-based study yet of blood proteins and future prostate cancer risk, with a focus on aggressive disease.

Twelve proteins were linked to prostate cancer diagnosed more than 15 years after blood collection, including GZMK, made by immune cells that recognize and destroy abnormal cells—suggesting immune activity may help suppress the disease long before diagnosis. Seven proteins were tied specifically to aggressive disease, including ANKRD1, consistently linked to cancers that had spread or proved fatal, along with markers tied to how cancer cells interact with surrounding tissue and how tumors recruit new blood vessels. Blood levels of proteins from known prostate cancer genes, including ERBB3, KRAS and NRAS, were also linked to aggressive disease diagnosed around a decade later—not evidence cancer was already present, but a possible clue to the biology that precedes it.

Zhe Huang, the study’s first author, said the findings reflect how varied the disease really is: “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.”

The team checked their results against other population studies and genetic evidence—some findings held up, others didn’t—and cautioned that none of the proteins are yet ready for clinical use, since most associations were modest.