A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer

// Jung Ku Jo 1, * , Jong Jin Oh 2, * , Yong Tae Kim 1 , Hong Sang Moon 3 , Hong Yong Choi 3 , Seunghyun Park 4 , Jin-Nyoung Ho 5 , Sungroh Yoon 4 , Hae Young Park 1 and Seok-Soo Byun 2 1 Department of Urology, Hanyang University Hospital, Seoul, Korea 2 Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 3 Department of Urology, Hanyang University Guri Hospital, Guri-si, Korea 4 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea 5 Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea * These authors contributed equally to this work Correspondence to: Seok-Soo Byun, email: ssbyun@snubh.org Hae Young Park, email: nopcme@hanyang.ac.kr Keywords: metastasis, prostate cancer, castration, genetic variation Received: December 14, 2016      Accepted: May 01, 2017      Published: May 30, 2017 ABSTRACT Background: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions: Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.