Germline Variation in HSD3B1 as a Novel Biomarker in Prostate Cancer
Abstract
In lay terms, we assessed the clinical impact of inheriting a variant form (allele) of the HSD3B1 gene, previously shown to enable prostate cancer cells to make their own derivative of testosterone that can drive disease progression, despite castration. We have demonstrated in three independent groups of men treated with androgen deprivation therapy (ADT) that men possessing the variant HSD3B1 allele have worse clinical outcomes (i.e. likelihood of disease progression, metastasis (spread to the bones or other distant sites), and death). Moreover, men who have two copies of the variant allele tend to have profound resistance to ADT. In a fourth cohort of men who received ADT for biochemical failure after initial radiation therapy, we again found that the variant allele predicts for large differences in time to metastasis. Taken together, these results indicate that HSD3B1 genotype is a powerful genetic biomarker of resistance to ADT, and can be used to identify men who might benefit from escalated treatment. Identification of these men has potential ramifications for guiding clinicians in augmenting standard ADT with highly-potent inhibitors of the androgen axis or chemotherapy in an effort to improve outcomes. Design and analysis of future studies should take into account HSD3B1 genotype, in view of the differences in outcomes according to the number of variant alleles a man inherits.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1043429
Entities
People
- Jason Hearn
- Nima Sharifi
Organizations
- University of Michigan