title: SNP Regulation of microRNA Expression and Subsequent Colon Cancer Risk.
abstract: BACKGROUND
  MicroRNAs (miRNAs) regulate messenger RNAs (mRNAs) and as such have been implicated in a variety of diseases, including cancer. MiRNAs regulate mRNAs through binding of the miRNA 5' seed sequence (~7-8 nucleotides) to the mRNA 3' UTRs; polymorphisms in these regions have the potential to alter miRNA-mRNA target associations. SNPs in miRNA genes as well as miRNA-target genes have been proposed to influence cancer risk through altered miRNA expression levels.
  
  
  METHODS
  MiRNA-SNPs and miRNA-target gene-SNPs were identified through the literature. We used SNPs from Genome-Wide Association Study (GWAS) data that were matched to individuals with miRNA expression data generated from an Agilent platform for colon tumor and non-tumor paired tissues. These samples were used to evaluate 327 miRNA-SNP pairs for associations between SNPs and miRNA expression levels as well as for SNP associations with colon cancer.
  
  
  RESULTS
  Twenty-two miRNAs expressed in non-tumor tissue were significantly different by genotype and 21 SNPs were associated with altered tumor/non-tumor differential miRNA expression across genotypes. Two miRNAs were associated with SNP genotype for both non-tumor and tumor/non-tumor differential expression. Of the 41 miRNAs significantly associated with SNPs all but seven were significantly differentially expressed in colon tumor tissue. Two of the 41 SNPs significantly associated with miRNA expression levels were associated with colon cancer risk: rs8176318 (BRCA1), ORAA 1.31 95% CI 1.01, 1.78, and rs8905 (PRKAR1A), ORGG 2.31 95% CI 1.11, 4.77.
  
  
  CONCLUSIONS
  Of the 327 SNPs identified in the literature as being important because of their potential regulation of miRNA expression levels, 12.5% had statistically significantly associations with miRNA expression. However, only two of these SNPs were significantly associated with colon cancer.
authors.affiliation: University of Utah, School of Medicine, Department of Internal Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Lila E
authors.initials: LE
authors.lastname: Mullany
authors.affiliation: University of Utah, School of Medicine, Department of Internal Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: University of Utah, School of Medicine, Department of Internal Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Buas
authors.affiliation: University of Utah, School of Medicine, Department of Internal Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs