Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Cohort and Clinical Data
4.2. Genetic Data
4.3. Outcomes
4.4. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Demographics at the Time of Initial Prostate Cancer Diagnosis | |
---|---|
Median age (years) | 64 (43–89) |
Median prostate-specific antigen (ng/dL) | 7 (0–3229) |
Stage | |
T1–T2b | 24 (28%) |
T2c | 25 (29%) |
T3+ | 38 (43%) |
N+ | 23 (38%) |
M+ | 18 (56%) |
Gleason grade | |
5–6 | 11 (13%) |
7 | 27 (31%) |
8–10 | 49 (56%) |
Radical prostatectomy | 51 (71%) |
Patient Characteristics at the Time of Initiation of Abiraterone Acetate and Prednisone for Castration-Resistant Stage | |
Median age (years) | 73 (54–90) |
Median prostate-specific antigen (ng/dL) | 66 (0–100) |
Median body mass index (kg/m2) | 30 (21–56) |
Bone metastases | 73 (84%) |
Soft tissue metastases | 43 (49%) |
Previous androgen-deprivation therapy | 87 (100%) |
Previous docetaxel | 56 (65%) |
Previous enzalutamide | 5 (6%) |
Previous cabazitaxel | 5 (6%) |
Time from initial diagnosis (years) | 8 (1–24) |
Patients alive at the time of data analysis | 38 (44%) |
SNP | n | Biochemical Response to Treatment | p | |
---|---|---|---|---|
Response Rates 1 | Effect Estimate | |||
rs2486758 | 87 | 50%/17% | OR 0.22 (0.07–0.63) | 0.005 |
rs4919685 | 87 | 38%/39% | OR 1.24 (0.64–2.40) | 0.524 |
rs17115100 | 87 | 40%/37% | OR 0.82 (0.31–2.19) | 0.689 |
rs743572 | 87 | 33%/40% | OR 1.13 (0.58–2.20) | 0.718 |
Time to Biochemical Progression | ||||
Median Time to Progression 1 | Effect Estimate | |||
rs2486758 | 87 | 7.0 months/2.9 months | HR 2.23 (1.39–3.56) | <0.001 |
rs4919685 | 87 | 3.5 months/4.6 months | HR 0.82 (0.47–1.42) | 0.429 |
rs17115100 | 87 | 4.5 months/5.3 months | HR 0.95 (0.67–1.35) | 0.693 |
rs743572 | 87 | 3.5 months/4.6 months | HR 1.03 (0.73–1.46) | 0.889 |
Model | n | Response to Treatment | p |
---|---|---|---|
Unadjusted | 87 | OR 0.22 (0.07–0.63) | 0.005 |
Age-adjusted (I) | 87 | OR 0.21 (0.07–0.62) | 0.005 |
Multivariable-adjusted (II) | 87 | OR 0.22 (0.07–0.63) | 0.005 |
Multivariable-adjusted (III) | 87 | OR 0.21 (0.07–0.62) | 0.005 |
Multivariable-adjusted (IV) | 87 | OR 0.18 (0.06–0.57) | 0.003 |
Time to Progression | |||
Unadjusted | 87 | HR 2.23 (1.39–3.56) | <0.001 |
Age-adjusted (I) | 87 | HR 2.22 (1.40–3.55) | 0.001 |
Multivariable-adjusted (II) | 87 | HR 2.26 (1.41–3.62) | 0.001 |
Multivariable-adjusted (III) | 87 | HR 2.29 (1.43–3.67) | 0.001 |
Multivariable-adjusted (IV) | 87 | HR 2.67 (1.64–4.36) | <0.001 |
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Binder, M.; Zhang, B.Y.; Hillman, D.W.; Kohli, R.; Kohli, T.; Lee, A.; Kohli, M. Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer. Int. J. Mol. Sci. 2016, 17, 1097. https://doi.org/10.3390/ijms17071097
Binder M, Zhang BY, Hillman DW, Kohli R, Kohli T, Lee A, Kohli M. Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer. International Journal of Molecular Sciences. 2016; 17(7):1097. https://doi.org/10.3390/ijms17071097
Chicago/Turabian StyleBinder, Moritz, Ben Y. Zhang, David W. Hillman, Rhea Kohli, Tanvi Kohli, Adam Lee, and Manish Kohli. 2016. "Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer" International Journal of Molecular Sciences 17, no. 7: 1097. https://doi.org/10.3390/ijms17071097