title: Association of polymorphisms in microRNA-binding sites and colorectal cancer in an Iranian population.
abstract: MicroRNAs (miRNAs) are agents of post-transcriptional gene expression, and they can affect many functions of an individual cell or tissue from extracellular matrix production to inflammatory processes and tumor development. We aimed to determine the possible role of miRNA-binding site polymorphisms located in five cancer-related genes: IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4 in colorectal cancer (CRC) risk modification in an Iranian population. This study was performed on 643 individuals (249 CRC cases and 394 healthy controls). We selected five cancer-related genes (IL-16, CDKN2A (p16), RAF1, PTGER4, and ITGB4) and investigated the genotypes of the 3' untranslated region miRNA-binding site polymorphisms in these genes in our study population. The restriction fragment length polymorphism results were confirmed by a direct sequencing method. We found a statistically significant difference between the rs1131445 polymorphism of the IL-16 gene and CRC. The frequencies of the genotypes TT, CT, and CC in controls were 51%, 40.4%, and 8.6%, respectively, and in cases were 41.4%, 44.1%, and 14.5%, respectively, which shows a significant association between the CC genotype of the rs1131445 polymorphism and CRC (P = 0.004). The frequency of the C allele in the CRC group was higher than in the controls, and the C allele of the rs1131445 polymorphism was found to be in association with CRC (P = 0.009). These associations remained significant after Bonferroni's correction for multiple testing. We found that the AA genotype of the rs743554 polymorphism in the ITGB4 gene and the T allele of the rs1051208 polymorphism of the RAF1 gene were associated with the risk of CRC in females; however, after Bonferroni's correction we found that they were non-significant. Finally, we can conclude that a significant relationship exists between the miRNA-binding site polymorphism of the IL-16 gene and CRC risk in the Iranian population.
authors.affiliation: Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Pedram
authors.initials: P
authors.lastname: Azimzadeh
authors.forename: Sara
authors.initials: S
authors.lastname: Romani
authors.forename: Seyed Reza
authors.initials: SR
authors.lastname: Mohebbi
authors.forename: Touraj
authors.initials: T
authors.lastname: Mahmoudi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Vahedi
authors.forename: Seyed Reza
authors.initials: SR
authors.lastname: Fatemi
authors.forename: Narges
authors.initials: N
authors.lastname: Zali
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zali
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D039663:Integrin beta4 / Q000235:genetics; D019410:Interleukin-16 / Q000235:genetics*; D007492:Iran; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C059834:ITGB4 protein, human; D039663:Integrin beta4; D019410:Interleukin-16; D035683:MicroRNAs; C545650:PTGER4 protein, human; D058309:Receptors, Prostaglandin E, EP4 Subtype; D019908:Proto-Oncogene Proteins c-raf