SpringerLink
Log in

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

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Quinn M, Babb P (2002) Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part II: individual countries. BJU Int 90(2):174–184

    Article  PubMed  CAS  Google Scholar 

  2. Edwards J, Krishna NS, Grigor KM et al (2003) Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 89(3):552–556

    Article  PubMed  CAS  Google Scholar 

  3. Fujimoto N, Miyamoto H, Mizokami A et al (2007) Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells. Cancer Invest 25(1):32–37

    Article  PubMed  CAS  Google Scholar 

  4. Arnold JT, Le H, McFann KK et al (2005) Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. Am J Physiol Endocrinol Metab, 288(3):E573–584

    Google Scholar 

  5. Shah S, Small E (2010) Emerging biological observations in prostate cancer. Expert Rev Anticancer Ther 10(1):89–101

    Article  PubMed  CAS  Google Scholar 

  6. D’Amico F, Biancolella M, Margiotti K et al (2007) Genomic biomarkers, androgen pathway and prostate cancer. Pharmacogenomics 8(6):645–661

    Article  PubMed  Google Scholar 

  7. Ross RW, Oh WK, **e W et al (2008) Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer. J Clin Oncol 26(6):842–847

    Article  PubMed  Google Scholar 

  8. Singh AS, Chau CH, Price DK et al (2005) Mechanisms of disease: polymorphisms of androgen regulatory genes in the development of prostate cancer. Nat Clin Pract Urol 2(2):101–107

    Article  PubMed  CAS  Google Scholar 

  9. Torkko KC, van Bokhoven A, Mai P et al (2008) VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men. Clin Cancer Res 14(10):3223–3229

    Article  PubMed  CAS  Google Scholar 

  10. Maeda O, Usami M (2005) Summary of General rules for clinical and pathological studies on prostate cancer (3rd edition). Nihon Rinsho 63(2):201–206

    PubMed  Google Scholar 

  11. Akaza H (2006) Trends in primary androgen depletion therapy for patients with localized and locally advanced prostate cancer: Japanese perspective. Cancer Sci 4:243–247

    Article  Google Scholar 

  12. De Coster R, Wouters W, Bruynseels J (1996) P450-dependent enzymes as targets for prostate cancer therapy. J Steroid Biochem Mol Biol, 56(1–6 Spec No):133–143

    Google Scholar 

  13. Attard G, Reid AH, A’Hern R et al (2009) Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 27(23):3742–3748

    Article  PubMed  CAS  Google Scholar 

  14. de Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. New Engl J Med 364(21):1995–2005

    Article  PubMed  Google Scholar 

  15. Reid AH, Attard G, Danila DC et al (2010) Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 28(9):1489–1495

    Article  PubMed  CAS  Google Scholar 

  16. Antognelli C, Mearini L, Talesa VN et al (2005) Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer. Prostate 63(3):240–251

    Article  PubMed  CAS  Google Scholar 

  17. Mononen N, Seppala EH, Duggal P et al (2006) Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors. Cancer Res 66(2):743–747

    Article  PubMed  CAS  Google Scholar 

  18. Habuchi T, Liqing Z, Suzuki T et al (2000) Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect. Cancer Res 60(20):5710–5713

    PubMed  CAS  Google Scholar 

  19. Kakinuma H, Tsuchiya N, Habuchi T et al (2004) Serum sex steroid hormone levels and polymorphisms of CYP17 and SRD5A2: implication for prostate cancer risk. Prostate Cancer Prostatic Dis 7(4):333–337

    Article  PubMed  CAS  Google Scholar 

  20. Peduzzi P, Concato J, Kemper E et al (1996) A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 49(12):1373–1379

    Article  PubMed  CAS  Google Scholar 

  21. Benjamini Y. Hochberg Y. (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc ser B, 57(1): 298–300

    Google Scholar 

  22. Attard G, Reid AH, Yap TA et al (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol, 26(28):4563–4571

    Google Scholar 

Download references

Acknowledgments

We thank the following investigators who participated in this study: Kensaku Nishimura (Osaka Rosai Hospital), Tsuneo Hara (Ikeda Municipal Hospital), Go Tanigawa (Osaka General Medical Center), and Toshiaki Yoshioka (Sumitomo Hospital).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan

    Takeshi Yamada, Tomohito Shimizu, Shinpei Nonen, Yasushi Fujio & Junichi Azuma

  2. Department of Urology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Masashi Nakayama, Yasutomo Nakai, Akihiko Okuyama & Norio Nonomura

  3. Department of Clinical Pharmacogenomics, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan

    Shinpei Nonen & Junichi Azuma

  4. Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Masashi Nakayama & Kazuo Nishimura

Authors
  1. Takeshi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masashi Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomohito Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinpei Nonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasutomo Nakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuo Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasushi Fujio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akihiko Okuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Junichi Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Norio Nonomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norio Nonomura.

About this article

Cite this article

Yamada, T., Nakayama, M., Shimizu, T. et al. 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. Int J Clin Oncol 18, 711–717 (2013). https://doi.org/10.1007/s10147-012-0430-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-012-0430-8

Keywords

Search

Navigation