The association between missense polymorphisms in SRD5A2 and HSD3B1 and treatment failure with abiraterone for castration-resistant prostate cancer.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
/ genetics
Aged
Aged, 80 and over
Alleles
Androstenes
/ therapeutic use
Genetic Association Studies
/ methods
Genotype
Humans
Male
Membrane Proteins
/ genetics
Middle Aged
Multienzyme Complexes
/ genetics
Polymorphism, Genetic
/ genetics
Progesterone Reductase
/ genetics
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Retrospective Studies
Steroid Isomerases
/ genetics
Treatment Failure
Journal
The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
17
06
2020
accepted:
27
01
2021
revised:
06
01
2021
pubmed:
3
3
2021
medline:
29
1
2022
entrez:
2
3
2021
Statut:
ppublish
Résumé
Missense polymorphism in HSD3B1, encoding 3β-hydroxysteroid dehydrogenase-1, was associated with outcome after abiraterone treatment. Other androgen-metabolizing enzymes may be involved in therapeutic effect in abiraterone. In this study, we investigated the significance of polymorphisms in genes involved in androgen and abiraterone metabolisms in prostate cancer patients treated with abiraterone. A total of 99 Japanese male castration-resistant prostate cancer patients treated with abiraterone between 2014 and 2018 were included. Genomic DNA was obtained from whole blood samples, and genotyping on SRD5A2 (rs523349), CYP17A1 (rs743572), CYP17A1 (rs2486758), and AKR1C3 (rs12529) was performed by PCR-based technique. Among the 99 patients, 32 (32.3%), 49 (49.5%), and 18 patients (18.2%) carried GG, GC, and CC alleles in SRD5A2, respectively. CC allele was associated with lower risk of treatment failure (hazard ratio, 0.43; 95% confidence interval, 0.20-0.87; P = 0.017) on multivariate analyses, compared with GG/GC alleles. In the combination model using HSD3B1 and SRD5A2 polymorphisms, compared with the combination of AA in HSD3B1 and GG/GC in SRD5A2, other combinations were associated with lower risk of treatment failure (hazard ratio, 0.34; 95% confidence interval, 0.17-0.62; P = 0.0003) on multivariate analyses. This study showed that SRD5A2 genetic variation was associated with the risk of treatment failure in abiraterone. Combinational use of genetic variation in HSD3B1 with SRD5A2 genetic variation augmented the ability of prognostic stratification.
Identifiants
pubmed: 33649516
doi: 10.1038/s41397-021-00220-0
pii: 10.1038/s41397-021-00220-0
doi:
Substances chimiques
3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
0
Androstenes
0
Membrane Proteins
0
Multienzyme Complexes
0
Progesterone Reductase
EC 1.1.1.145
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
EC 1.3.99.5
SRD5A2 protein, human
EC 1.3.99.5
Steroid Isomerases
EC 5.3.3.-
abiraterone
G819A456D0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
440-445Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
Références
Shiota M, Yokomizo A, Naito S. Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer. Endocr Relat Cancer. 2012;19:R243–53.
doi: 10.1530/ERC-12-0232
Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68:4447–54.
doi: 10.1158/0008-5472.CAN-08-0249
Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008;68:6407–15.
doi: 10.1158/0008-5472.CAN-07-5997
Nacusi LP, Tindall DJ. Targeting 5α-reductase for prostate cancer prevention and treatment. Nat Rev Urol. 2011;8:378–84.
doi: 10.1038/nrurol.2011.67
Price DK, Chau CH, Till C, Goodman PJ, Leach RJ, Johnson-Pais TL, et al. Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial. Cancer. 2016;122:2332–40.
doi: 10.1002/cncr.30071
Makridakis N, Ross RK, Pike MC, Chang L, Stanczyk FZ, Kolonel LN, et al. A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase. Cancer Res. 1997;57:1020–2.
pubmed: 9067262
Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Itsumi M, Inokuchi J, et al. SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy. Eur J Cancer. 2015;51:1962–9.
doi: 10.1016/j.ejca.2015.06.122
Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Kashiwagi E, Dejima T, et al. The prognostic impact of serum testosterone during androgen-deprivation therapy in patients with metastatic prostate cancer and the SRD5A2 polymorphism. Prostate Cancer Prostatic Dis. 2016;19:191–6.
doi: 10.1038/pcan.2016.2
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.
doi: 10.1056/NEJMoa1704174
James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.
doi: 10.1056/NEJMoa1702900
Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, et al. Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature. 2015;523:347–51.
doi: 10.1038/nature14406
Shiota M, Narita S, Akamatsu S, Fujimoto N, Sumiyoshi T, Fujiwara M, et al. Association of missense polymorphism in HSD3B1 with outcomes among men with prostate cancer treated with androgen-deprivation therapy or abiraterone. JAMA Netw Open. 2019;2:e190115.
doi: 10.1001/jamanetworkopen.2019.0115
Li Z, Alyamani M, Li J, Rogacki K, Abazeed M, Upadhyay SK, et al. Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy. Nature. 2016;533:547–51.
doi: 10.1038/nature17954
International Union Against Cancer. Urologic tumors. Prostate. In: Sobin LH, Wittekind CH (editors). TNM classification of malignant tumors. 5th ed. New York: John Wiley & Sons; 1997. p. 170–3.
Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59.
doi: 10.1200/JCO.2007.12.4487
Shiota M, Fujimoto N, Imada K, Yokomizo A, Itsumi M, Takeuchi A, et al. Potential role for YB-1 in castration-resistant prostate cancer and resistance to enzalutamide through the androgen receptor V7. J Natl Cancer Inst. 2016;108:djw005.
doi: 10.1093/jnci/djw005
Shiota M, Fujimoto N, Itsumi M, Takeuchi A, Inokuchi J, Tatsugami K, et al. Gene polymorphisms in antioxidant enzymes correlate with the efficacy of androgen-deprivation therapy for prostate cancer with implications of oxidative stress. Ann Oncol. 2017;28:569–75.
doi: 10.1093/annonc/mdw646
Binder M, Zhang BY, Hillman DW, Kohli R, Kohli T, Lee A, et al. Common genetic variation in CYP17A1 and response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Int J Mol Sci. 2016;17:E1097.
doi: 10.3390/ijms17071097
McKay RR, Werner L, Mostaghel EA, Lis R, Voznesensky O, Zhang Z, et al. A phase II trial of abiraterone combined with dutasteride for men with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2017;23:935–45.
doi: 10.1158/1078-0432.CCR-16-0987