Gene Variant Seen to Promote Castration-resistant Disease in Whites

Gene Variant Seen to Promote Castration-resistant Disease in Whites
A variant in a gene that promotes the production of testosterone by prostate cancer cells is linked to poorer survival and the development of castration-resistant disease in Caucasians with metastatic prostate cancer, a study suggests. Its researchers recommend that genetic testing be part of routine care for patients, as those with this variant may need more aggressive treatment. The study, "HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer," was published in the journal JAMA Oncology. The growth of many prostate cancers is driven by signaling from male hormones, most notably testosterone. Treatment with androgen deprivation therapy (ADT), where testosterone levels are lowered by means of surgical or chemical castration, is often effective. But some tumors become castration-resistant, and no longer respond to ADT. One common way castration resistance develops is when tumor cells start making their own testosterone, and are no longer dependent on testosterone from elsewhere. This process is heavily reliant on an enzyme coded by the gene HSD3B1. A variant in this gene, HSD3B1(1245C) is associated with higher testosterone production. As such, it has been proposed that HSD3B1(1245C) could predispose certain individuals to castration-resistant cancer that is harder to treat. Researchers at the Cleveland Clinic and colleagues tested this idea using data from the Phase 3 trial (NCT00309985), called CHAARTED, in which men with metastatic prostate cancer who still responded to ADT were randomly assigned to ADT with or without the chemotherapy agent docetaxel. They looked at data for 475 patients — all white, average age of 63. Of them, 270 had at least one copy of the HSD3B1(1245C) variant (each person inherits o
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