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Joint effects of inflammation and androgen metabolism on prostate cancer severity
Author(s) -
Rebbeck Timothy R.,
Rennert Hanna,
Walker Amy H.,
Panossian Saarene,
Tran Teo,
Walker Kyle,
Spangler Elaine,
PatacsilCoomes Margerie,
Sachdeva Rajeev,
Wein Alan J.,
Malkowicz S. Bruce,
ZeiglerJohnson Charnita
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23687
Subject(s) - prostate cancer , prostate , androgen , medicine , hyperplasia , inflammation , cancer , carcinogenesis , oncology , cancer research , endocrinology , hormone
Abstract 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. © 2008 Wiley‐Liss, Inc.