HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer

Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small.

To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer).

Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor.

The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.