CYP3A4 genetic variant and disease-free survival among white and black men after radical prostatectomy.
OBJECTIVE
Prostate cancer is an androgen sensitive disease. Cytochrome P450 3A4 (CYP3A4) oxidatively deactivates testosterone by converting it to biologically less active metabolites. Previous studies suggest that a germline genetic variant in the 5' regulatory region of the gene may interfere with deactivation and increase the risk of clinically advanced prostate cancer. We investigated the impact of this polymorphism on the risk of recurrence after prostatectomy.


METHODS
We assembled clinical data and analyzed specimens from a large series of patients who underwent prostatectomy who were carefully staged at a single institution and had 5 to 10 years of prospective clinical followup. The series included 428 white men and 309 black men.


RESULTS
Stage, Gleason score or preoperative prostate specific antigen strongly predicted progression-free survival (PFS) but were not associated with CYP3A4 genotypes. There was a strong association between race and genotype (p = 0.00002) in that 8% of white men and 83% of black men had 1 or more copies of the G allele. When both races were included genotype was associated with PFS (hazard ratio [HR] 1.27, CI 1.08-1.27, p = 0.005). In race specific analyses increasing copies of the G allele were associated with poorer PFS among white men (HR 1.98, CI 1.06-3.70, p = 0.03) but had little impact on PFS among black men (HR 1.004, CI 0.77-1.32, p = 0.97).


CONCLUSIONS
The CYP3A4 genotype studied was not associated with pathological features of prostate cancer for men of either race. Unstratified analyses of men of both races and stratified analyses of white men demonstrated poorer PFS after prostatectomy for those with the G allele, but the G allele did not predict PFS among black men.
Powell
Isaac J
IJ
Barbara Ann Karmanos Cancer Institute, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. ipowell@med.wayne.edu
Zhou
Junying
J
Sun
Yezhou
Y
Sakr
Wael A
WA
Patel
N P
NP
Heilbrun
Lance K
LK
Everson
Richard B
RB
D000368:Aged; D044383:Black People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D044465:White People
D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human