Journal Article

Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer

Debora Landi, Federica Gemignani, Alessio Naccarati, Barbara Pardini, Pavel Vodicka, Ludmila Vodickova, Jan Novotny, Asta Försti, Kari Hemminki, Federico Canzian and Stefano Landi

in Carcinogenesis

Volume 29, issue 3, pages 579-584
Published in print March 2008 | ISSN: 0143-3334
Published online January 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm304
Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer

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Recent evidence indicate that small non-coding RNA molecules, called micro-RNAs (miRNAs), can bind to the 3′ untranslated regions (UTRs) of messenger RNAs and interfere with their translation, thereby regulating cell growth, differentiation, apoptosis and tumorigenesis. Genetic polymorphisms can reside on miRNA-binding sites. Thus, it is conceivable that the miRNA regulation may be affected by polymorphisms on the 3′ UTRs. Since gene deregulation is one of the key mechanisms by which cells can progress to cancer, we hypothesize that common polymorphisms within miRNA-target binding sites could play a role in the individual risk of cancer. In the present study, we selected the 3′ UTRs of 104 genes candidate for colorectal cancer (CRC) and we identified putative miRNA-binding sites by specialized algorithms (PicTar, DianaMicroT, miRBase, miRanda, TargetScan and microInspector). Fifty-seven single-nucleotide polymorphisms (SNPs) were identified in miRNA-binding sites. We evaluated the SNPs for their ability to affect the binding of the miRNA with its target, by assessing the variation of Gibbs free energy between the two alleles of each SNP. We found eight common polymorphisms that were further investigated by a case–control association studies. The study was carried out on a series of cases and controls from Czech Republic, a population with the highest worldwide incidence of CRC. We found statistically significant associations between risk of CRC and variant alleles of CD86 [odds ratio (OR) = 2.74; 95% confidence interval (CI) = 1.24–6.04, for the variant homozygotes] and INSR genes (OR = 1.94; 95% CI = 1.03–3.66, for the variant homozygotes). These results are the first reporting positive association between miRNA-binding SNPs sequences and cancer risk.

Journal Article.  5032 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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