Prostate Cancer Coverage from Every Angle

Is Testosterone-Related Genetic Variant Linked to Poor Outcomes in Men With Prostate Cancer?

By: Sara Tewksbury
Posted: Monday, March 30, 2020

Nima Sharifi, MD, of Cleveland Clinic’s Lerner Research Institute, and colleagues have identified a potential connection between a testosterone-related genetic variant called HSD3B1(1245C) and a more aggressive disease with shorter survival in men with metastatic prostate cancer. More specifically, men with low-volume metastatic disease who had the adrenal-permissive genotype had inferior outcomes. The trial’s findings were published in JAMA Oncology.

“These findings lay the groundwork for more personalized and effective treatments for prostate cancer,” said Dr. Sharifi in a Cleveland Clinic news release. “If men carry this specific testosterone-related genetic abnormality, we may be able to individualize their therapy.”

The researchers analyzed data from 475 participants and looked at the efficacy of androgen-deprivation therapy alone or in combination with docetaxel in men with metastatic prostate cancer. They studied the outcomes of men who carried the genetic variant as well as those who did not. Of the 475 patients, 270 had the HSD3B1(1245C) allele.

Patients with the genetic variant experienced aggressive disease progression, treatment resistance, and poor outcomes. “Freedom from castration-resistant prostate cancer at 2 years was diminished in men with low-volume disease with the adrenal-permissive versus adrenal-restrictive genotype (51.0% vs. 70.5%; P = .01),” they reported. In addition, overall survival at 5 years was also worse in these men (57.5% vs. 70.8%; P = .03). However, the genetic variant HSD3B1(1245C) did not influence the clinical outcomes in men with high-volume prostate cancer.

Dr. Sharifi and colleagues concluded that the inheritance of the adrenal-permissive HSD3B1 genotype may be connected to earlier castration resistance and shorter overall survival. The findings from this study show that the genetic variant may be used to calculate the risk of men with low-volume metastatic prostate cancer. Those results could assist clinicians in counseling patients regarding treatment options.

Disclosure: For full disclosures of the study authors, visit

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