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Title

Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H

AuthorsNaranjo, Silvia ; Alonso, M. Eva; Manzanares, Miguel; Gavilán, Angela; Gómez-Skarmeta, José Luis ; Houlston, Richard S.
Issue DateSep-2010
PublisherPublic Library of Science
CitationPLoS Genetics 6(9): e1001126 (2010)
AbstractCommon genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.
Description9 páginas, 5 figuras.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pgen.1001126
URIhttp://hdl.handle.net/10261/27794
DOI10.1371/journal.pgen.1001126
ISSN1553-7390
E-ISSN1553-7404
Appears in Collections:(CABD) Artículos
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