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- Title
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.
- Authors
Yamada, Takeshi; Nakayama, Masashi; Shimizu, Tomohito; Nonen, Shinpei; Nakai, Yasutomo; Nishimura, Kazuo; Fujio, Yasushi; Okuyama, Akihiko; Azuma, Junichi; Nonomura, Norio
- Abstract
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). Conclusion: The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.
- Subjects
PROSTATE cancer treatment; GENETIC polymorphisms; STEROID hormones; CANCER relapse; JAPANESE people; ANDROGENS; HORMONE therapy; CANCER invasiveness; DISEASES
- Publication
International Journal of Clinical Oncology, 2013, Vol 18, Issue 4, p711
- ISSN
1341-9625
- Publication type
Article
- DOI
10.1007/s10147-012-0430-8