Dataset Information

Racial differences in prostate inflammation: results from the REDUCE study.

ABSTRACT: Prostate cancer (PC) risk differs between races, and we previously showed prostate inflammation in benign prostate tissue was linked with a lower future PC risk. However, whether prostate tissue inflammation varies by race is unknown. We analyzed baseline acute and chronic prostate inflammation by race in REDUCE, a 4-year, multicenter, placebo-controlled study where all men had a negative prostate biopsy prior to enrollment. We included 7,982 men with standardized central pathology review to determine the presence or absence of chronic or acute inflammation in baseline prostate biopsy tissue. Logistic regression was used to compare prostate inflammation by race, adjusting for confounders. Of 7,982 men, 7,271 were white (91.1%), 180 (2.3%) black, 131 (1.6%) Asian, 319 (4.0%) Hispanic and 81 (1%) unknown. A total of 78% had chronic and 15% had acute inflammation. On multivariable analysis relative to white men, black men were less likely (OR = 0.65, 95%CI: 0.41-1.03, p = 0.07) and Asian men more likely to have acute inflammation (OR = 1.74, 95%CI: 1.14-2.65, p = 0.001). Hispanic men had similar levels of acute inflammation as white men. Chronic inflammation did not significantly differ across races. We identified racial differences in acute inflammation, particularly in Asian men, in benign prostate tissue that inversely mirrored population-level data on PC race disparity. As we showed in REDUCE that acute inflammation is linked with lower future PC risk, if validated in future studies, these data suggest racial differences in prostatic acute inflammation may contribute in part to race differences in PC risk, especially among Asian men.

SUBMITTER: Vidal AC

PROVIDER: S-EPMC5641057 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Racial differences in prostate inflammation: results from the REDUCE study.

Vidal Adriana C AC Chen Zinan Z Howard Lauren E LE Moreira Daniel M DM Castro-Santamaria Ramiro R Andriole Gerald L GL Taioli Emanuela E Fowke Jay H JH Knudsen Beatrice B Drake Charles G CG Nickel J Curtis JC Freedland Stephen J SJ

Oncotarget 20160718 42

Prostate cancer (PC) risk differs between races, and we previously showed prostate inflammation in benign prostate tissue was linked with a lower future PC risk. However, whether prostate tissue inflammation varies by race is unknown. We analyzed baseline acute and chronic prostate inflammation by race in REDUCE, a 4-year, multicenter, placebo-controlled study where all men had a negative prostate biopsy prior to enrollment. We included 7,982 men with standardized central pathology review to det ...[more]

PMID: 29069714

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Project description: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.

Project description:ImportanceWhile racial disparities in prostate cancer mortality are well documented, it is not well known how these disparities vary geographically within the US.ObjectiveTo characterize geographic variation in prostate cancer-specific mortality differences between black and white men.Design, setting, and participantsThis cohort study included data from 17 geographic registries within the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2007, to December 31, 2014. Inclusion criteria were men 18 years and older with biopsy-confirmed prostate cancer. Men missing data on key variables (ie, cancer stage, Gleason grade group, prostate-specific antigen level, and survival follow-up data) were excluded. Analysis was performed from September 5 to December 25, 2018.ExposurePatient SEER-designated race (ie, black, white, or other).Main outcomes and measuresFine and Gray competing-risks regression analyses were used to evaluate the difference in prostate-cancer specific mortality between black and white men. A stratified analysis by Gleason grade group was performed stratified as grade group 1 and grade groups 2 through 5.ResultsThe final cohort consisted of 229 771 men, including 178 204 white men (77.6%), 35 006 black men (15.2%), and 16 561 men of other or unknown race (7.2%). Mean (SD) age at diagnosis was 64.9 (8.8) years. There were 4773 prostate cancer deaths among white men and 1250 prostate cancer deaths among black men. Compared with white men, black men had a higher risk of mortality overall (adjusted hazard ratio [AHR], 1.39 [95% CI, 1.30-1.48]). In the stratified analysis, there were 4 registries in which black men had worse prostate cancer-specific survival in both Gleason grade group 1 (Atlanta, Georgia: AHR, 5.49 [95% CI, 2.03-14.87]; Greater Georgia: AHR, 1.88 [95% CI, 1.10-3.22]; Louisiana: AHR, 1.80 [95% CI, 1.06-3.07]; New Jersey: AHR, 2.60 [95% CI, 1.53-4.40]) and Gleason grade groups 2 through 5 (Atlanta: AHR, 1.88 [95% CI, 1.46-2.45]; Greater Georgia: AHR, 1.29 [95% CI, 1.07-1.56]; Louisiana: AHR, 1.28 [95% CI, 1.07-1.54]; New Jersey: AHR, 1.52 [95% CI, 1.24-1.87]), although the magnitude of survival difference was lower than for Gleason grade group 1 in each of these registries. The greatest race-based survival difference for men with Gleason grade group 1 disease was in the Atlanta registry.Conclusions and relevanceThese findings suggest that population-level differences in prostate cancer survival among black and white men were associated with a small set of geographic areas and with low-risk prostate cancer. Targeted interventions in these areas may help to mitigate prostate cancer care disparities at the national level.

Project description:PurposeA recent meta-analysis showed that aspirin was associated with reduced prostate cancer risk. As anti-inflammatory medications lower PSA levels, whether these findings reflect reduced prostate cancer detection or lower prostate cancer risk is unknown. We tested the association between aspirin and nonaspirin NSAID use on prostate cancer diagnosis in REDUCE, where all men received biopsies at 2 and 4 years largely independent of PSA. REDUCE tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative prestudy biopsy.Experimental designWe examined the association between aspirin, NSAIDs, or both and total, low-grade (Gleason < 7), or high-grade (Gleason ≥ 7) prostate cancer versus no prostate cancer using multinomial logistic regression among 6,390 men who underwent ≥1 on-study biopsy. Multivariable analyses were adjusted for age, race, geographic region, PSA, prostate volume, digital rectal examination, body mass index, treatment arm, smoking, alcohol, statins, hypertension, diabetes, and cardiovascular disease.ResultsOverall, 3,169 men (50%) were nonusers, 1,368 (21%) used aspirin, 1,176 (18%) used NSAIDs, and 677 (11%) used both. In unadjusted models, aspirin was associated with reduced prostate cancer risk (OR = 0.85, P = 0.036). In multivariable analyses, aspirin was associated with reduced total prostate cancer risk (OR = 0.81, P = 0.015). Use of NSAIDs or NSAIDs and aspirin was not associated with total, low-grade, or high-grade prostate cancer, though all ORs were <1 (all P ≥ 0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID users versus nonusers. On multivariable analysis, the use of aspirin and/or NSAIDs was significantly associated with decreased total (OR = 0.87, P = 0.030) and high-grade (OR = 0.80, P = 0.040), but not with low-grade, prostate cancer risk (OR = 0.90, P = 0.15). Results were similar in placebo and dutasteride arms.ConclusionsAmong men with a negative biopsy, aspirin and/or NSAID use was associated with decreased prostate cancer risk. Additional studies are warranted.

Dataset Information

Racial differences in prostate inflammation: results from the REDUCE study.

Publications

Racial differences in prostate inflammation: results from the REDUCE study.

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