title: Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival.
abstract: Background:MicroRNAs (miRNAs) mediate negative regulation of target genes through base pairing, and aberrant miRNA expression has been described in cancers. We hypothesized that single nucleotide polymorphisms (SNPs) within miRNA target sites might influence clinical outcomes in patients with colorectal cancer.Methods:Sixteen common SNPs within miRNA target sites were identified, and the association between these SNPs and overall survival was assessed in colorectal cancer patients using Kaplan-Meier analysis, Cox regression model, and survival tree analysis.Results:Survival tree analysis identified a higher-order genetic interaction profile consisting of theRPS6KB1rs1051424 andZNF839rs11704 that was significantly associated with overall survival. The 5-year survival rates were 74.6%, 62.7%, and 57.1% for the low-, medium-, and high-risk genetic profiles, respectively (P= 0.006). The genetic interaction profile remained significant even after adjusting for potential risk factors. Additionalin silicoanalysis provided evidence that rs1051424 and rs11704 affectRPS6KB1andZNF839expressions, which in turn is significantly correlated with prognosis in colorectal cancer.Conclusion:Our results suggest that the genetic interaction profiles among SNPs within miRNA target sites might be prognostic markers for colorectal cancer survival.
authors.affiliation: Department of Pharmacy, Zhongxiao Branch, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Ying-Pi
authors.initials: YP
authors.lastname: Yang
authors.affiliation: Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.; Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ting
authors.affiliation: Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Chen
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.; 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
mesh_terms: D000368:Aged; D001665:Binding Sites; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics; D016019:Survival Analysis
chemical_list: D035683:MicroRNAs; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: colorectal cancer; genetic interaction.; microRNAs; single nucleotide polymorphism; survival