The association of polymorphism in gonadotropin releasing hormone with serum testosterone level during androgen-deprivation therapy and prognosis in metastatic prostate cancer.

Abstract

e16570 Background: Serum testosterone suppression during androgen-deprivation therapy (ADT) have been reported to affect ADT efficacy. However, the factor affecting hormonal variations during ADT was less explored. Therefore, in this study, we investigated the missense polymorphisms in gonadotropin releasing hormone (GNRH) and hormonal variations during ADT as well as the prognosis among men treated with primary ADT for metastatic prostate cancer. Methods: This study included 80 Japanese patients with metastatic prostate cancer, whose serum testosterone levels during ADT were available. The association of the GNRH1 gene polymorphism (rs6185, S20W) and the GNRH2 gene polymorphism (rs6051545, A16V) with clinicopathological parameters including serum testosterone levels during ADT as well as the prognosis including progression-free survival and overall survival was examined. Results: The CT allele and the CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone levels during ADT compared with the CC allele. Consequently, the CT alleles was associated with higher progression risk after adjustment with age and serum testosterone levels during ADT [hazard ratio (95% confidence interval), 1.73 (1.00-3.00), P = 0.049]. Conclusions: Taken together, these findings suggested that genetic variation in rs6051545 ( GNRH2) may result in the inadequate suppression of on serum testosterone during ADT, which may lead to detrimental effect of ADT on prognosis among men with metastatic prostate cancer.