Identification of candidate genes carrying polymorphisms associated with the risk of colorectal cancer by analyzing the colorectal mutome and microRNAome
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22282400
DOI
10.1002/cncr.27435
Knihovny.cz E-resources
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Haplotypes MeSH
- Risk Assessment MeSH
- Polymorphism, Single Nucleotide * MeSH
- Colorectal Neoplasms genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- MicroRNAs analysis MeSH
- Multivariate Analysis MeSH
- Mutation * MeSH
- Odds Ratio MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- MicroRNAs MeSH
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.
References provided by Crossref.org
Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer
