Journal Article

Polymorphisms in miRNA-binding sites of nucleotide excision repair genes and colorectal cancer risk

Alessio Naccarati, Barbara Pardini, Landi Stefano, Debora Landi, Jana Slyskova, Jan Novotny, Miroslav Levy, Veronika Polakova, Ludmila Lipska and Pavel Vodicka

in Carcinogenesis

Volume 33, issue 7, pages 1346-1351
Published in print July 2012 | ISSN: 0143-3334
Published online May 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs172
Polymorphisms in miRNA-binding sites of nucleotide excision repair genes and colorectal cancer risk

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Reduced DNA repair capacity and DNA damage accumulation may lead to cancer development. Regulation of and coordination between genes involved in DNA repair pathways is fundamental for maintaining genome stability, and post-transcriptional gene regulation by microRNAs (miRNAs) may therefore be of particular relevance. In this context, the presence of single nucleotide polymorphisms (SNPs) within the 3ʹuntranslated regions of target DNA repair genes could alter the binding with specific miRNAs, modulating gene expression and ultimately affecting cancer susceptibility.

In this study, we investigated the role of genetic variations in miRNA-binding sites of nucleotide excision repair (NER) genes in association with colorectal cancer (CRC) risk. From 28 NER genes, we screened among SNPs residing in their 3ʹuntranslated regions and simultaneously located in miRNA-binding sites, with an in silico approach. Through the calculation of different binding free energy according to both alleles of identified SNPs, and with global binding free energies median providing a threshold, we selected nine NER gene variants. We tested those SNPs in 1098 colorectal cancer cases and 1469 healthy controls from the Czech Republic.

Rs7356 in RPA2 and rs4596 in GTF2H1 were associated with colorectal cancer risk. After stratification for tumor location, the association of both SNPs was significant only for rectal cancer (rs7356: OR 1.52, 95% CI 1.02–2.26, P = 0.04 and rs4596: OR 0.69, 95% CI 0.50–0.94, P = 0.02; results not adjusted for multiple testing).

Variation in miRNA target binding sites in the 3ʹuntranslated region of NER genes may be important for modulating colorectal cancer risk, with a different relevance according to tumor location.

Journal Article.  5386 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.