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2014-11-06

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cc-by (c) Fortini, Barbara K. et al., 2014
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/67497

Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype

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Recurs relacionat

http://dx.doi.org/10.1371/journal.pone.0111914

Resum

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification of a number of common variants associated with modest risk. Several risk variants map within the vicinity of TGFβ/BMP signaling pathway genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an enhancer element in SMAD7 intron 4. In this study, we show that four SNPs including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific enhancer effects in a large, multi-component enhancer of SMAD7. All four SNPs demonstrate allele-specific protein binding to nuclear extracts of CRC cell lines. Furthermore, some of the risk-associated alleles correlate with increased expression of SMAD7 in normal colon tissues. Finally, we show that the enhancer is responsive to BMP4 stimulation. Taken together, we propose that the associated CRC risk at 18q21.1 is due to four functional variants that regulate SMAD7 expression and potentially perturb a BMP negative feedback loop in TGFβ/BMP signaling pathways.

Matèries

Càncer colorectal, Genètica, Cromosomes humans

Matèries (anglès)

Colorectal cancer, Genetics, Human chromosomes

Citació

Col·leccions

Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

FORTINI, Barbara K., et al. Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype. PLoS One. 2014. Vol. 9, num. 11, pags. e111914. ISSN 1932-6203. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/67497

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