title: Prediagnostic circulating markers of inflammation and risk of prostate cancer.
abstract: Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies evaluating this association using C-reactive protein (CRP) and interleukin-6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) with the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow-up period of 24 years (21-26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and the risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated prediagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95% confidence interval [CI] = 1.10-2.29, p-trend = 0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were 1.08 (95% CI: 0.74-1.60, p-trend = 0.56) and 1.25 (95% CI: 0.87-1.81, p-trend = 0.14), respectively. Men with elevated leukocyte counts had a 2.57-fold (95% CI: 0.99-6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider combining at least two markers or using an inflammation score derived from many inflammatory markers to evaluate prostate cancer risk.
authors.affiliation: Department of Surgery, Division of Public Health Sciences, Washington, University School of Medicine, St Louis, MO; Siteman Cancer Center, Washington, University School of Medicine, St Louis, MO.
authors.forename: Adetunji T
authors.initials: AT
authors.lastname: Toriola
authors.forename: Jari A
authors.initials: JA
authors.lastname: Laukkanen
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kurl
authors.forename: Kristiina
authors.initials: K
authors.lastname: Nyyssönen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Ronkainen
authors.forename: Jussi
authors.initials: J
authors.lastname: Kauhanen
mesh_terms: D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D005387:Finland; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000209:etiology; D012306:Risk
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: C-reactive protein; fibrinogen; inflammation; leukocyte count; prostate cancer