The role of inflammation in the pathogenesis of prostate cancer.
OBJECTIVE
A new hypothesis for the etiology of prostate cancer is that chronic or recurrent prostate inflammation may initiate and promote prostate cancer development.


METHODS
We reviewed the current direct and indirect evidence from epidemiology, genetics, molecular biology and histopathology implicating inflammation in the pathogenesis of prostate cancer.


RESULTS
The case for prostate inflammation as a cause of prostate cancer is compelling. Epidemiology data have correlated prostatitis and sexually transmitted infections with increased prostate cancer risk and intake of anti-inflammatory drugs and antioxidants with decreased prostate cancer risk. Genetic studies have identified RNASEL, encoding an interferon inducible ribonuclease, and MSR1, encoding subunits of the macrophage scavenger receptor, as candidate inherited susceptibility genes for familial prostate cancer. Somatic silencing of GSTP1, encoding a glutathione S-transferase capable of defending against oxidant cell and genome damage, has been found in almost all prostate cancer cases. Proliferative inflammatory atrophy lesions containing activated inflammatory cells and proliferating epithelial cells appear likely to be precursors to prostatic intraepithelial neoplasia lesions and prostatic carcinomas.


CONCLUSIONS
Emerging hints that prostate inflammation may contribute to prostatic carcinogenesis will provide opportunities for the discovery and development of new drugs and strategies for prostate cancer prevention.
Nelson
William G
WG
Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. bnelson@jhmi.edu
De Marzo
Angelo M
AM
DeWeese
Theodore L
TL
Isaacs
William B
WB
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics; D000975:Antioxidants / Q000627:therapeutic use; D018833:Chaperonins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D011472:Prostatitis / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D011971:Receptors, Immunologic / Q000235:genetics; D051116:Receptors, Scavenger; D012307:Risk Factors; D051117:Scavenger Receptors, Class A
C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D000217:Acyltransferases; C043403:fatty acyl ethyl ester synthase; D018833:Chaperonins