https://scholars.lib.ntu.edu.tw/handle/123456789/584561
標題: | Genetic variants in nuclear factor-kappa B binding sites are associated with clinical outcomes in prostate cancer patients | 作者: | Huang S.-P. Lin V.C. Lee Y.-C. Yu C.-C. CHAO-YUAN HUANG Chang T.-Y. Lee H.-Z. Juang S.-H. Lu T.-L. Bao B.-Y. |
關鍵字: | NF-κB; Outcomes; Prostate cancer; Single-nucleotide polymorphism | 公開日期: | 2013 | 卷: | 49 | 期: | 17 | 起(迄)頁: | 3729-3737 | 來源出版物: | European Journal of Cancer | 摘要: | Nuclear factor-kappa B (NF-κB) transcription factors have been suggested to be involved in prostate cancer progression. Activated NF-κB translocates to the nucleus, binds to NF-κB binding sites and regulates target gene expression, leading to the given physiological response. It was hypothesised that the sequence variants in NF-κB binding sites might affect prostate cancer progression. We systematically evaluated 15 single-nucleotide polymorphisms (SNPs) within NF-κB binding sites those were predicted using a genome-wide database in a cohort of 1024 prostate cancer patients. Associations of these SNPs with prostate cancer characteristics and clinical outcomes after radical prostatectomy (RP) for localised disease, and after androgen-deprivation therapy (ADT) for advanced disease were assessed by Kaplan-Meier analysis and Cox regression model. We found that PSMD7 rs2387084 and MYCN rs1429409 were significantly related to earlier onset of prostate cancer and advanced clinical stage, respectively. No SNPs were significantly associated with disease recurrence after RP. Four and three SNPs were notably associated with prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM), respectively, after ADT. LSAMP rs13088089, CCL17 rs223899, PSMD7 rs2387084 and MON1B rs284924 remained the significant predictors for PCSM whilst PSMD7 rs2387084 remained a significant predictor for ACM in multivariate models including clinical predictors. Moreover, we also noted that there were strong effects of the combined genotype on PCSM and patients with a greater number of unfavourable genotypes had a shorter time to PCSM during ADT (P for trend < 0.001). It was concluded that SNPs inside NF-κB binding sites might be useful to improve outcome prediction in prostate cancer patients. ? 2013 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84886773109&doi=10.1016%2fj.ejca.2013.07.012&partnerID=40&md5=aad64a4cb801bd06bb06e1e91b61edca https://scholars.lib.ntu.edu.tw/handle/123456789/584561 |
ISSN: | 0959-8049 | DOI: | 10.1016/j.ejca.2013.07.012 | SDG/關鍵字: | immunoglobulin enhancer binding protein; adult; aged; androgen deprivation therapy; article; binding site; cancer mortality; cancer patient; Ccl17 gene; cohort analysis; gene; gene expression; genetic association; genetic variability; genotype; human; Kaplan Meier method; LSAMP gene; major clinical study; male; multivariate analysis; MYCN gene; nucleotide sequence; priority journal; prognosis; proportional hazards model; prostate cancer; prostatectomy; PSMD7 gene; single nucleotide polymorphism; NF-κB; Outcomes; Prostate cancer; Single-nucleotide polymorphism; Aged; Binding Sites; Cohort Studies; Humans; Male; Middle Aged; NF-kappa B; Nuclear Proteins; Oncogene Proteins; Polymorphism, Single Nucleotide; Prognosis; Prostatic Neoplasms; Proteasome Endopeptidase Complex; Protein Binding |
顯示於: | 醫學系 |
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