title: MicroRNA polymorphisms and risk of colorectal cancer.
abstract: BACKGROUND
  miRNAs act as post-transcriptional regulators of gene expression. Genetic variation in miRNA-encoding sequences or their corresponding binding sites may affect the fidelity of the miRNA-mRNA interaction and subsequently alter the risk of cancer development.
  
  
  METHODS
  This study expanded the search for miRNA-related polymorphisms contributing to the etiology of colorectal cancer across the genome using a novel platform, the Axiom miRNA Target Site Genotyping Array (237,858 markers). After quality control, the study included 596 cases and 429 controls from the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study of colorectal cancer in northern Israel. The association between each marker and colorectal cancer status was examined assuming a log-additive genetic model using logistic regression adjusted for sex, age, and two principal components.
  
  
  RESULTS
  Twenty-three markers had P values less than 5.0E-04, and the most statistically significant association involved rs2985 (chr6:34845648; intronic of UHRF1BP1; OR = 0.66; P = 3.7E-05). Furthermore, this study replicated a previously published risk locus, rs1051690, in the 3'-untranslated region of the insulin receptor gene INSR (OR = 1.38; P = 0.03), with strong evidence of differences in INSR gene expression by genotype.
  
  
  CONCLUSIONS
  This study is the first to examine associations between genetic variation in miRNA target sites and colorectal cancer using a genome-wide approach. Functional studies to identify allele-specific effects on miRNA binding are needed to confirm the regulatory capacity of genetic variation to influence risk of colorectal cancer.
  
  
  CONCLUSIONS
  This study demonstrates the potential for an miRNA-targeted genome-wide association study to identify candidate susceptibility loci and prioritize them for functional characterization.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schmit
authors.affiliation: Affymetrix, Incorporated, Santa Clara, California.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gollub
authors.affiliation: Affymetrix, Incorporated, Santa Clara, California.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shapero
authors.affiliation: USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel.
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.affiliation: Affymetrix, Incorporated, Santa Clara, California.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finn
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. Clalit Health Services National Cancer Control Center, Haifa, Israel. Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California. sgruber@usc.edu.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D035683:MicroRNAs