한국인의 전이성전립선암에서 유전자 변이 (SLC28A3

Abstract

Purpose: Metastasis in prostate cancer (PCa) is associated with worse clinical outcomes. In addition, metastatic PCa can demonstrate progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). In this study, we aimed to assess genetic variants in metastatic PCa and the relationship of single nucleotide polymorphisms (SNPs) associated with metastatic disease with progression to CRPC. Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 SNPs on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 104 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 after correction for multiple testing, and analyzed the relationship between these SNPs and time to CRPC in metastatic PCa. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with metastatic PCa. The five polymorphisms among these 42 most strongly associated with metastatic PCa were rs2241714, rs143790069, rs72821581, rs75992542 and rs56350726. In addition, one of these SNPs, rs56350726 was significantly associated with time to CRPC in Kaplan-Meier analysis (Log rank test, p = 0.019). Conclusions: The five SNPs most strongly associated with metastatic PCa were rs2241714 rs143790069, rs72821581, rs75992542, rs56350726. One SNP in SLC28A3 (rs56350726) associated with metastatic PCa was also found to have a significant relationship with progression to CRPC among patients who were treated with hormone therapy.