title: Genetic variants in ultraconserved regions associate with prostate cancer recurrence and survival.
abstract: Ultraconserved regions (UCRs) are DNA segments of longer than 200 bp in length that are completely conserved between human, rat, and mouse genomes. Recent studies have shown that UCRs are frequently located at fragile sites involved in cancers, and their levels of transcription can be altered during human tumorigenesis. We systematically evaluated 14 common single-nucleotide polymorphisms (SNPs) within UCRs in three cohorts of prostate cancer patients, to test the hypothesis that these UCR SNPs might influence clinical outcomes. Examination using multivariate analysis adjusted for known clinicopathologic factors found association between rs8004379 and recurrence in localized disease [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.91, P = 0.015], which was confirmed in the replication set (HR 0.70, 95% CI 0.51-0.96, P = 0.027). Remarkably, a consistent association of rs8004379 with a decreased risk for prostate cancer-specific mortality was also observed in the advanced prostate cancer patient group (HR 0.48, 95% CI 0.32-0.70, P < 0.001). Additional in silico analysis suggests that rs8004379 tends to affect NPAS3 expression, which in turn was found to be correlated with patient prognosis. In conclusion, our findings suggest that SNPs within UCRs may be valuable prognostic biomarkers for assessing prostate cancer treatment response and survival.
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.|Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.|Department of Nursing, Asia University, Taichung, Taiwan.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
authors.affiliation: Department of Urology, E-Da Hospital, Kaohsiung, Taiwan.|School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lin
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pharmacy, Tajen University, Pingtung, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yin
authors.affiliation: Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan.
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Te-Ling
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Linsen Chinese Medicine Branch, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Jiunn-Bey
authors.initials: JB
authors.lastname: Pao
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
mesh_terms: D000368:Aged; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D059248:Chemoradiotherapy / Q000379:methods; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009419:Nerve Tissue Proteins / Q000235:genetics; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D051381:Rats; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C502963:NPAS3 protein, human