Genetic variants in microRNAs and microRNA target sites predict biochemical recurrence after radical prostatectomy in localized prostate cancer
Journal
International Journal of Cancer
Journal Volume
135
Journal Issue
11
Pages
2661-2667
Date Issued
2014
Author(s)
Huang S.-P.
Levesque E.
Guillemette C.
Yu C.-C.
Lin V.C.
Chung I.-C.
Chen L.-C.
Laverdi?re I.
Lacombe L.
Fradet Y.
Chang T.-Y.
Lee H.-Z.
Juang S.-H.
Bao B.-Y.
Abstract
Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single-nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan'Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16'2.21, p for trend50.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15'2.08, p for trend50.004) and in combined analysis (HR 1.57, 95% CI 1.26'1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and micro-RNA target sites can be predictive biomarkers for BCR after RP. ? 2014 UICC.
Subjects
Biochemical recurrence; microRNA; Prostate cancer; Radical prostatectomy; Single-nucleotide polymorphism
SDGs
Other Subjects
biological marker; microRNA; microRNA 181c; microRNA 5007; microRNA 605; unclassified drug; luciferase; microRNA; tumor marker; 3' untranslated region; allele; Article; Asian; biochemical recurrence; cancer localization; cancer prognosis; cancer recurrence; cancer risk; cancer staging; carcinogenesis; Caucasian; CDON gene; cohort analysis; controlled study; dose response; follow up; gene replication; genetic association; genetic variability; genotype; Gleason score; hazard ratio; human; human cell; Kaplan Meier method; major clinical study; male; MIR605 gene; MTRR gene; prediction; priority journal; proportional hazards model; prostate cancer; prostatectomy; protein targeting; retrospective study; RNA binding; RNA targeting site; single nucleotide polymorphism; trend study; aged; Asian continental ancestry group; genetics; metabolism; Neoplasm Recurrence, Local; pathology; Prostatic Neoplasms; Aged; Asian Continental Ancestry Group; European Continental Ancestry Group; Follow-Up Studies; Humans; Luciferases; Male; MicroRNAs; Neoplasm Recurrence, Local; Polymorphism, Single Nucleotide; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Tumor Markers, Biological
Publisher
Wiley-Liss Inc.
Type
journal article