Abstract
Background: Prostate cancer 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 prostate cancer risk.Methods: Seven thousand nonHispanic white men were enrolled in the REduction by DUtasteride of prostate Cancer Events (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 prostate cancer 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 [odds ratio (OR), 1.77; 95% confidence interval (CI), 1.51-2.08] and Australia/New Zealand (OR, 2.07; 95% CI, 1.40-3.06). Men from these regions had lower prostate cancer risk than Europeans at biopsy. Among North Americans, prevalence of acute inflammation was higher in Canada versus the United States (OR, 1.40; 95% CI, 1.07-1.83), but prostate cancer 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 prostate cancer risk at biopsy.Conclusions: Prevalence of histologic prostate inflammation varied by region. Geographic differences in prostate inflammation tracked inversely with geographic differences in prostate cancer risk.Impact: Characterization of premalignant prostate biology and the relationship with subsequent prostate cancer risk could inform prostate cancer prevention efforts. Cancer Epidemiol Biomarkers Prev; 27(7); 783-9. ©2018 AACR.
Highlights
Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in higherresource countries [1]
Prevalence of histologic prostate inflammation varied by region
Causes are not well understood, but a case-control study nested within the Prostate Cancer Prevention Trial (PCPT) reported that serum omega-3 and omega-6 fatty acid levels were associated with histologic prostate inflammation [3]
Summary
Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in higherresource countries [1]. While much of this variation can be explained by differences in prostatespecific antigen (PSA) screening, geographic variation in incidence rates was noted prior to the PSA screening era. Using data from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, we reported that current smokers were more likely to have histologic prostate inflammation than non-smokers [7], while statin users were less likely to have histologic prostate inflammation than non-users [8] Together, these studies suggest that lifestyle factors influence histologic prostate inflammation which, in turn, may affect prostate cancer risk [9]. We examined geographic differences in prevalence of histologic prostate inflammation and subsequent PC risk
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