Joint effects of inflammation and androgen metabolism on prostate cancer severity
Timothy R Rebbeck, Hanna Rennert, Amy H Walker, Saarene Panossian, Teo Tran, Kyle Walker, Elaine Spangler, Margerie Patacsil-Coomes, Rajeev Sachdeva, Alan J Wein, S Bruce Malkowicz, Charnita Zeigler-Johnson
First publication: 19 Jun 2008
PMID: 18566991 PMCID: PMC2700293 DOI: 10.1002/ijc.23687
Multiple pathways of prostate carcinogenesis have been proposed, including those involving androgen metabolism and inflammation. These pathways are not independent, and may act together in prostate cancer etiology: androgens promote both inflammatory processes and serve as mitogens in prostate tumor growth. To explore the possible joint effects of these pathways in prostate cancer severity, we studied 1,090 Caucasian prostate cancer cases to evaluate whether tumor severity is influenced by a history of benign prostatic hyperplasia (BPH) interacting with genotypes involved in inflammation or androgen metabolism including MSR1, RNASEL, AR, CYP3A4, CYP3A43, CYP3A5 and SRD5A2. We observed a statistically significant interaction between a number of genotypes and BPH. After considering the potential for false positive associations, the only remaining significant associations involved CYP3A43 P340A genotypes and history of BPH on both Gleason grade (interaction p-value = 0.026) and tumor stage (interaction p-value = 0.017). These results suggest that androgen metabolism may act in concert with inflammatory phenotypes such as BPH in determining prostate cancer severity.
Copyright 2008 Wiley-Liss, Inc.
Full text: 10.1002/ijc.23687
Please contact us if you are having difficulty accessing the full PDF of this or any MADCaP publication.