A Genetic Variant in SLC28A3, Rs56350726, is Associated with Progression to Castration-resistant Prostate Cancer in a Korean Population with Metastatic Prostate Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 13

PMID 29228579

Citations 3

Authors

Jung Ki Jo

Jong Jin Oh

Yong Tae Kim

Hong Sang Moon

Hong Yong Choi

SeungHyun Park

Jin-Nyoung Ho

Sungroh Yoon

Hae Young Park

Seok-Soo Byun

Affiliations

Soon will be listed here.

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, = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, = 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.

Citing Articles

Impact of genetic variants in the solute carrier () genes encoding drug uptake transporters on the response to anticancer chemotherapy.

Marin J, Serrano M, Herraez E, Lozano E, Ortiz-Rivero S, Perez-Silva L Cancer Drug Resist. 2024; 7:27.

PMID: 39143954 PMC: 11322974. DOI: 10.20517/cdr.2024.42.

Analysis of genetic biomarkers, polymorphisms in ADME-related genes and their impact on pharmacotherapy for prostate cancer.

Rehman K, Iqbal Z, Zhiqin D, Ayub H, Saba N, Khan M Cancer Cell Int. 2023; 23(1):247.

PMID: 37858151 PMC: 10585889. DOI: 10.1186/s12935-023-03084-5.

Genetic Polymorphisms and Pharmacotherapy for Prostate Cancer.

Shiota M, Akamatsu S, Narita S, Terada N, Fujimoto N, Eto M JMA J. 2021; 4(2):99-111.

PMID: 33997443 PMC: 8119070. DOI: 10.31662/jmaj.2021-0004.

References

Badagnani I, Chan W, Castro R, Brett C, Huang C, Stryke D . Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 2005; 5(3):157-65. DOI: 10.1038/sj.tpj.6500303. View

Knudsen K, Scher H . Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res. 2009; 15(15):4792-8. PMC: 2842118. DOI: 10.1158/1078-0432.CCR-08-2660. View

Damaraju S, Zhang J, Visser F, Tackaberry T, Dufour J, Smith K . Identification and functional characterization of variants in human concentrative nucleoside transporter 3, hCNT3 (SLC28A3), arising from single nucleotide polymorphisms in coding regions of the hCNT3 gene. Pharmacogenet Genomics. 2005; 15(3):173-82. DOI: 10.1097/01213011-200503000-00006. View

Park K, Han S, Whang Y, Lee H, Yoo Y, Lee J . Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population. Cancer Genet Cytogenet. 2006; 169(1):39-44. DOI: 10.1016/j.cancergencyto.2006.03.012. View

Smaletz O, Scher H, Small E, Verbel D, McMillan A, Regan K . Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J Clin Oncol. 2002; 20(19):3972-82. DOI: 10.1200/JCO.2002.11.021. View

Gundem G, Van Loo P, Kremeyer B, Alexandrov L, Tubio J, Papaemmanuil E . The evolutionary history of lethal metastatic prostate cancer. Nature. 2015; 520(7547):353-357. PMC: 4413032. DOI: 10.1038/nature14347. View

Vollmer R, Kantoff P, Dawson N, Vogelzang N . A prognostic score for hormone-refractory prostate cancer: analysis of two cancer and leukemia group B studies. Clin Cancer Res. 1999; 5(4):831-7. View

Wu A, Whittemore A, Kolonel L, Stanczyk F, John E, Gallagher R . Lifestyle determinants of 5alpha-reductase metabolites in older African-American, white, and Asian-American men. Cancer Epidemiol Biomarkers Prev. 2001; 10(5):533-8. View

Lee S, Im S, Park Y, Woo S, Kim S, Choi M . Genetic polymorphisms of SLC28A3, SLC29A1 and RRM1 predict clinical outcome in patients with metastatic breast cancer receiving gemcitabine plus paclitaxel chemotherapy. Eur J Cancer. 2013; 50(4):698-705. DOI: 10.1016/j.ejca.2013.11.028. View

10.

Hong M, Macintyre G, Wedge D, Van Loo P, Patel K, Lunke S . Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat Commun. 2015; 6:6605. PMC: 4396364. DOI: 10.1038/ncomms7605. View

11.

Berger M, Lawrence M, Demichelis F, Drier Y, Cibulskis K, Sivachenko A . The genomic complexity of primary human prostate cancer. Nature. 2011; 470(7333):214-20. PMC: 3075885. DOI: 10.1038/nature09744. View

12.

James N, Sydes M, Clarke N, Mason M, Dearnaley D, Spears M . Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016; 387(10024):1163-77. PMC: 4800035. DOI: 10.1016/S0140-6736(15)01037-5. View

13.

Tomioka S, Shimbo M, Amiya Y, Nakatsu H, Murakami S, Shimazaki J . Outcome of patients with hormone-refractory prostate cancer: prognostic significance of prostate-specific antigen-doubling time and nadir prostate-specific antigen. Jpn J Clin Oncol. 2008; 38(1):36-42. DOI: 10.1093/jjco/hym153. View

14.

Epstein J, Allsbrook Jr W, Amin M, Egevad L . The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005; 29(9):1228-42. DOI: 10.1097/01.pas.0000173646.99337.b1. View

15.

Kwak C, Jeong S, Park M, Lee E, Lee S . Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer. J Urol. 2002; 168(3):995-1000. DOI: 10.1016/S0022-5347(05)64559-4. View

16.

Wyatt A, Mo F, Wang Y, Collins C . The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing. Asian J Androl. 2013; 15(3):301-8. PMC: 3739651. DOI: 10.1038/aja.2013.13. View

17.

Joshi G, Singh P, Negi A, Rana A, Singh S, Kumar R . Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents. Chem Biol Interact. 2015; 240:120-33. DOI: 10.1016/j.cbi.2015.08.009. View

18.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

19.

Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Itsumi M, Inokuchi J . SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy. Eur J Cancer. 2015; 51(14):1962-9. DOI: 10.1016/j.ejca.2015.06.122. View

20.

van Houten M, Gooren L . Differences in reproductive endocrinology between Asian men and Caucasian men--a literature review. Asian J Androl. 2001; 2(1):13-20. View