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Page 245 Huang et al. J Transl Genet Genom 2021;5:240-9 https://dx.doi.org/10.20517/jtgg.2021.14

Table 2. Summary of studies about the association between HSD3B1 variants and PCa treated with other medical management
Medical No. of No. of
Study Results Conclusions
management Cases Carriers
[29]
Almassi et al. , 2018 Ketoconazole 90 46 For duration of treatment: The HSD3B1(1245C) variant allele is
CC: HR = 2.2; 95%CI: 1.1-4.4; P = associated with prolonged time to disease
0.02 progression among men with metastatic
AC: HR = 1.8; 95%CI: 1.1-2.9; P = CRPC treated with nonsteroidal CYP17A1
0.01 inhibition
For disease progression:
CC: HR = 0.5; 95%CI: 0.3-1.1; P =
0.08
AC: HR = 0.6; 95%CI: 0.4-1.0; P
= 0.06
Hahn, et al. [30] , 2018 Abiraterone 76 34 For PFS: Variant HSD3B1 caused no difference with
CC vs. AA: 6.4 m vs. 7.3 m; P = the response to abiraterone
0.28
CA vs. AA: 6.2 m vs. 7.3 m; P =
0.64
[19]
Shiota et al. , 2019 Abiraterone 99 14 For treatment failure: Variant HSD3B1 was associated with less
AC: HR = 0.35; 95%CI: 0.13- treatment failure and better survival
0.80; P = 0.01 outcome for CRPC treated with abiraterone
For OS:
AC: HR = 0.40; 95%CI: 0.13-
0.94; P = 0.04
Hearn et al. [21] , 2020 ADT randomized 475 270 Data not shown Variant HSD3B1 did not appear to be
plus docetaxel predictive of differential benefit with
docetaxel
Khalaf et al.[31], 2020 Abiraterone or 546 297 For TTP: HSD3B1 (CC) was associated with shorter
enzalutamide CC: HR = 1.31; 95%CI: 1.02-1.67; TTP and less response rate, but not with
P = 0.032 survival outcome
For PSA response:
CC vs. AC vs. AA: 48% vs. 62%
vs. 65%; P = 0.019
For TTPP:
CC: HR = 1.28; 95%CI: 0.99-1.66;
P = 0.064
[32]
Lu et al. , 2020 Abiraterone or 266 123 For PSA30 response: HSD3B1 (CC) was associated with shorter
enzalutamide CC vs. AC/AA: 67.7% vs. 68.4%; overall survival, but not with response to
P > 0.99 treatment
For duration of treatment:
CC: HR = 1.25; 95%CI: 0.79-1.97;
P = 0.34
For OS:
CC: HR = 1.78; 95%CI: 1.03-3.07;
P = 0.04
HR: Hazard ratio; 95%CI: 95% confidence interval; CRPC: castrate-resistant prostate cancer; PFS: progression-free survival; OS: overall survival;
TTP: time to progression; PSA: prostate specific antigen.

Both Khalaf et al. and Lu et al. investigated the association between HSD3B1 and
[31]
[32]
[31]
abiraterone/enzalutamide. In the work of Khalaf et al. , 547 patients from two cohorts were involved. For
patients with metastatic CRPC treated with abiraterone/enzalutamide, the CC genotype had worse time to
progression (HR = 1.31; P = 0.032) and a nonsignificant trend to shorter time to PSA progression (HR =
1.28; P = 0.064). In addition, the CC genotype was less likely to achieve a PSA response according to the
PSA response rates (48% for CC, 62% for AC, and 65% for AA, P = 0.019). However, no association was
shown between HSD3B1(1245C) and overall survival. In contrast, Lu et al. proposed that HSD3B1 (CC)
[32]
was related to worse survival outcome (HR = 1.78; P = 0.04) and had no association with response to
management in patients with mCRPC treated with abiraterone/enzalutamide according to the analysis of a
cohort of 266 patients.