Genetic variants in ultraconserved regions associate with prostate cancer recurrence and survival
Journal
Scientific Reports
Journal Volume
6
Pages
22124
Date Issued
2016
Author(s)
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. ? 2016, Nature Publishing Group. All rights reserved.
SDGs
Other Subjects
nerve protein; NPAS3 protein, human; transcription factor; aged; animal; cell culture; chemoradiotherapy; cohort analysis; conserved sequence; gene expression regulation; genetics; human; Kaplan Meier method; male; middle aged; mortality; mouse; multivariate analysis; outcome assessment; procedures; prognosis; proportional hazards model; Prostatic Neoplasms; rat; single nucleotide polymorphism; statistics and numerical data; survival rate; tumor recurrence; Aged; Animals; Cells, Cultured; Chemoradiotherapy; Cohort Studies; Conserved Sequence; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; Mice; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Nerve Tissue Proteins; Outcome Assessment (Health Care); Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Rats; Survival Rate; Transcription Factors
Publisher
Nature Publishing Group
Type
journal article