title: Identification of candidate genes carrying polymorphisms associated with the risk of colorectal cancer by analyzing the colorectal mutome and microRNAome.
abstract: BACKGROUND
  The presence of single-nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of genes could affect the binding between a microRNA (miRNA) and its target, with consequences on gene expression regulation. Considering the important role of miRNAs in carcinogenesis, it is hypothesized here that these SNPs could also affect the individual risk of colorectal cancer (CRC).
  
  
  METHODS
  To test this hypothesis, a list was developed of 140 somatically mutated genes deduced from previous works on the mutome of the CRC. A further selection was conducted of SNPs within target sites for miRNAs that are expressed only in the colorectum (the colorectal microRNAome) and having adequate population frequencies. This yielded 12 SNPs that were genotyped in a case-control association study on 717 colorectal cases and 1171 controls from the Czech Republic.
  
  
  RESULTS
  Statistically significant associations were found between the risk of CRC and the variant alleles of KIAA0182 (rs709805) (odds ratio = 1.57; 95% confidence interval = 1.06-2.78, for the variant homozygotes) and NUP210 genes (rs354476) (odds ratio = 1.36; 95% confidence interval = 1.02-1.82, for the variant homozygotes).
  
  
  CONCLUSIONS
  The results support the study hypothesis and highlight the importance of SNPs within miRNA-dependent regulatory regions. Further studies on the role exerted by NUP210 and KIAA0182 in colorectal carcinogenesis are warranted.
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Landi
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Sonia
authors.initials: S
authors.lastname: Garritano
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D035683:MicroRNAs