A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer
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Jung Ki Jo1,*, Jong Jin Oh2,*, Yong Tae Kim1, Hong Sang Moon3, Hong Yong Choi3, Seunghyun Park4, Jin-Nyoung Ho5, Sungroh Yoon4, Hae Young Park1 and Seok-Soo Byun2
1Department of Urology, Hanyang University Hospital, Seoul, Korea
2Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
3Department of Urology, Hanyang University Guri Hospital, Guri-si, Korea
4 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea
5Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea
*These authors contributed equally to this work
Seok-Soo Byun, email: [email protected]
Hae Young Park, email: [email protected]
Keywords: metastasis, prostate cancer, castration, genetic variation
Received: December 14, 2016 Accepted: May 01, 2017 Published: May 30, 2017
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.
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