Joint effects of inflammation and androgen metabolism on prostate cancer severity.
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.
Rebbeck
Timothy R
TR
Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. rebbeck@mail.med.upenn.edu
Rennert
Hanna
H
Walker
Amy H
AH
Panossian
Saarene
S
Tran
Teo
T
Walker
Kyle
K
Spangler
Elaine
E
Patacsil-Coomes
Margerie
M
Sachdeva
Rajeev
R
Wein
Alan J
AJ
Malkowicz
S Bruce
SB
Zeigler-Johnson
Charnita
C
D000728:Androgens / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D008297:Male; D011230:Precancerous Conditions / Q000209:etiology / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000473:pathology*
D000728:Androgens; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human