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Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):847-56. doi: 10.1158/1055-9965.EPI-13-1126. Epub 2014 Apr 18.

Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial.

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1
Authors' Affiliations: Departments of Pathology and Immunology; The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore; Division of Cancer Prevention, Department of Health and Human Services, National Cancer Institute, NIH, Bethesda, Maryland; University of Colorado School of Medicine, Aurora, Colorado; Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas; SWOG Statistical Center; Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Moores Cancer Center, University of California San Diego, La Jolla, California; and Division of Public Health Sciences and The Alvin J. Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Abstract

BACKGROUND:

Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.

METHODS:

Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.

RESULTS:

Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy).

CONCLUSION:

Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias.

IMPACT:

This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation.

PMID:
24748218
PMCID:
PMC4012292
DOI:
10.1158/1055-9965.EPI-13-1126
[Indexed for MEDLINE]
Free PMC Article
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