Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy.
BACKGROUND
Hormone ablation therapy is the standard therapy for prostate cancer; however, there are large individual differences in the duration of response to the therapy. We investigated, in this retrospective multicenter study, the association between genetic polymorphic variations in steroidogenesis-related genes and the risk of progression to castration-resistant prostate cancer (CRPC) in Japanese patients after androgen deprivation therapy.


METHODS
Two hundred and fourteen Japanese patients with prostate cancer who were receiving androgen deprivation therapy were enrolled in this study. We investigated 22 single-nucleotide polymorphisms (SNPs) from 8 genes related to steroidogenesis. The SNPs were assayed by polymerase chain reaction (PCR)-based methods. The different genotypes in this cohort were analyzed according to a case-control status of progression to CRPC at the median duration of hormonal therapy. A logistic regression method with adjustments for patients' characteristics was applied for the analysis.After applying the logistic regression method, we performed Cox regression analysis, following Kaplan-Meier and log-rank analyses.


RESULTS
In the logistic regression analysis four genetic polymorphisms, rs743572, rs6162, rs6163, and rs1004467, in the CYP17A1 gene were significantly associated with a risk of progression to CRPC (p < 0.05). Cox regression analysis for these SNPs showed an association of risk of progression to CRPC with the rs743572 genotype (p = 0.02, odds ratio [OR] 0.43, 95 % confidence interval [CI] 0.22-0.85).


CONCLUSIONS
The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Takeshi
T
Yamada
Masashi
M
Nakayama
Tomohito
T
Shimizu
Shinpei
S
Nonen
Yasutomo
Y
Nakai
Kazuo
K
Nishimura
Yasushi
Y
Fujio
Akihiko
A
Okuyama
Junichi
J
Azuma
Norio
N
Nonomura
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D012189:Retrospective Studies; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D016896:Treatment Outcome
D000726:Androgen Antagonists; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase