Inflammatory serum markers and risk and severity of prostate cancer: The PROCA‐life study

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive‐CRP (hs‐CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA‐life), a prospective population‐based cohort study, 7,356 men were included. Prediagnostic WBC and hs‐CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow‐up. During a mean 11.8 years follow‐up, 509 men developed prostate cancer (mean age at diagnosis 71.7 years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs‐CRP), a combined score based on analyte tertiles (score range 2–6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose–response relationship between hs‐CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00–1.07. Men with an increase in hs‐CRP between two measurements (Δhs‐CRP) of ≥1.00 mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02–1.82), compared to men with no change or decrease in hs‐CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04–2.73) compared to men with lower scores. Our study supports that hs‐CRP including repeated measurements alone or in combination with WBC may be a useful inflammation‐related biomarker for prostate cancer risk and prognosis. What's new? Although chronic inflammation likely influences prostate cancer development, a clear association is yet to be established. In particular, uncertainties remain regarding the relationship between systemic inflammatory markers and prostate cancer. In this investigation of data for more than 7,350 men, pre‐diagnostic levels of C‐reactive protein (CRP), measured via high‐sensitivity CRP (hs‐CRP) testing at study entry and at follow‐up, were associated with a dose‐response increase in prostate cancer risk. Risk and disease severity were further associated with a combined score incorporating both hs‐CRP and white blood cell count, highlighting the relevance of inflammation in prostate cancer development and prognosis.