HSD3B1 Allele Inheritance Linked With ADT Resistance

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The HSD3B1 (1245C) allele is linked to androgen deprivation therapy resistance among patients with prostate cancer.
The HSD3B1 (1245C) allele is linked to androgen deprivation therapy resistance among patients with prostate cancer.

The HSD3B1 (1245C) allele is linked to androgen deprivation therapy (ADT) resistance among patients with prostate cancer, according to a study published in The Lancet Oncology.1

Researchers conducted a multicohort study that retrospectively examined 443 men who were treated with ADT for biochemical failure or non-metastatic clinical failure and who had the HSD3B1 allele.

Multivariable analyses were conducted to determine the independent predictive value of the genotype on patient outcomes, specifically progression-free survival.

The researchers found that, in the primary study cohort that included 118 patients who underwent prostatectomy, median progression-free survival decreased with respect to the number of variant alleles inherited, with 6.6 years in men with homozygous wild-type genotype, 4.1 years with heterozygous variant genotype, and 2.5 years with homozygous variant genotype.

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Regarding the homozygous wild-type genotype, inheriting 1 or 2 copies of the variant allele was predictive of lower progression-free survival.

Findings were independently confirmed in validation cohorts, with similar results for distant metastasis-free survival and overall survival.

Reference

  1. Hearn JW, AbuAli G, Reichard CA, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol. 2016. doi: 10.1016/S1470-2045(16)30227-3 [Epub ahead of print]

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