The association between missense polymorphisms in SRD5A2 and HSD3B1 and treatment failure with abiraterone for castration-resistant prostate cancer.
Pharmacogenomics J
; 21(4): 440-445, 2021 08.
Article
de En
| MEDLINE
| ID: mdl-33649516
ABSTRACT
Missense polymorphism in HSD3B1, encoding 3ß-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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Polymorphisme génétique
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Progesterone reductase
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Steroid isomerases
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase
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Tumeurs prostatiques résistantes à la castration
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Androstènes
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Protéines membranaires
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Complexes multienzymatiques
Type d'étude:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limites:
Aged
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Aged80
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Humans
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Male
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Middle aged
Langue:
En
Journal:
Pharmacogenomics J
Sujet du journal:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
Japon