Geographic differences in baseline prostate inflammation and relationship with subsequent prostate cancer risk: results from the multinational REDUCE trial

Background: Prostate cancer (PC) incidence rates vary 25-fold worldwide. Differences in PSA screening are largely, but not entirely, responsible. We examined geographic differences in prevalence of histologic prostate inflammation and subsequent PC risk. Methods: 7,000 non-Hispanic white men were enrolled in the REDUCE trial from Europe (n=4,644), North America (n=1,746), South America (n=466), and Australia/New Zealand (n=144). Histologic inflammation in baseline negative prostate biopsies was classified as chronic (lymphocytes/macrophages) or acute (neutrophils). Multivariable logistic regression was used to examine associations between region and prostate inflammation, and between region and PC risk at 2-year biopsy. Results: Prevalence of prostate inflammation varied across region, with broadly similar patterns for acute and chronic inflammation. Relative to Europe, prevalence of acute inflammation was higher in North America (OR 1.77; 95%CI 1.51-2.08) and Australia/New Zealand (OR 2.07; 95%CI 1.40-3.06). Men from these regions had lower PC risk than Europeans at biopsy. Among North Americans, prevalence of acute inflammation was higher in Canada versus the US (OR 1.40; 95%CI 1.07-1.83), but PC risk did not differ between these regions. Among Europeans, prevalence of acute inflammation was lower in Northern and Eastern (OR 0.79; 95%CI 0.65-0.97 and OR 0.62; 95%CI 0.45-0.87, respectively), relative to Western Europe, and these men had higher PC risk at biopsy. Conclusions: Prevalence of histologic prostate inflammation varied by region. Geographic differences in prostate inflammation tracked inversely with geographic differences in PC risk. Impact: Characterization of premalignant prostate biology and the relationship with subsequent prostate cancer risk could inform prostate cancer prevention efforts.