International Journal of Clinical Oncology

, Volume 18, Issue 4, pp 711–717

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

  • Takeshi Yamada
  • Masashi Nakayama
  • Tomohito Shimizu
  • Shinpei Nonen
  • Yasutomo Nakai
  • Kazuo Nishimura
  • Yasushi Fujio
  • Akihiko Okuyama
  • Junichi Azuma
  • Norio Nonomura
Original Article

DOI: 10.1007/s10147-012-0430-8

Cite this article as:
Yamada, T., Nakayama, M., Shimizu, T. et al. Int J Clin Oncol (2013) 18: 711. doi:10.1007/s10147-012-0430-8

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.

Keywords

Prostate cancer Pharmacogenomics Androgen deprivation therapy SNPs CYP17A1 

Copyright information

© Japan Society of Clinical Oncology 2012

Authors and Affiliations

  • Takeshi Yamada
    • 1
  • Masashi Nakayama
    • 2
    • 4
  • Tomohito Shimizu
    • 1
  • Shinpei Nonen
    • 1
    • 3
  • Yasutomo Nakai
    • 2
  • Kazuo Nishimura
    • 4
  • Yasushi Fujio
    • 1
  • Akihiko Okuyama
    • 2
  • Junichi Azuma
    • 1
    • 3
  • Norio Nonomura
    • 2
  1. 1.Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical SciencesOsaka UniversitySuitaJapan
  2. 2.Department of Urology, Graduate School of MedicineOsaka UniversitySuitaJapan
  3. 3.Department of Clinical Pharmacogenomics, School of PharmacyHyogo University of Health SciencesKobeJapan
  4. 4.Department of UrologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan