Dataset Information

Geographic Differences in Baseline Prostate Inflammation and Relationship with Subsequent Prostate Cancer Risk: Results from the Multinational REDUCE Trial.

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.

SUBMITTER: Allott EH

PROVIDER: S-EPMC6035080 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Geographic Differences in Baseline Prostate Inflammation and Relationship with Subsequent Prostate Cancer Risk: Results from the Multinational REDUCE Trial.

Allott Emma H EH Markt Sarah C SC Howard Lauren E LE Vidal Adriana C AC Moreira Daniel M DM Castro-Santamaria Ramiro R Andriole Gerald L GL Mucci Lorelei A LA Freedland Stephen J SJ

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180418 7

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 = ...[more]

PMID: 29669727

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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:BACKGROUND & AIMS:Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation. METHODS:We conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B6, B12, D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFN?, TNF?, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation. RESULTS:In models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (-14.9 cells/mm3, 95% CI: -27.9, -1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status. CONCLUSIONS:In summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.

Dataset Information

Geographic Differences in Baseline Prostate Inflammation and Relationship with Subsequent Prostate Cancer Risk: Results from the Multinational REDUCE Trial.

Publications

Geographic Differences in Baseline Prostate Inflammation and Relationship with Subsequent Prostate Cancer Risk: Results from the Multinational REDUCE Trial.

Similar Datasets

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