Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
dc.contributor.author | Le Marchand, Loic | |
dc.date.accessioned | 2016-04-29T20:56:02Z | |
dc.date.available | 2016-04-29T20:56:02Z | |
dc.date.issued | 2014-09 | |
dc.description.abstract | <p>Note: A full list of authors and affiliations appears at the end of the article.</p> <p>GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the ‘iCOGS’ genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval = 0.84-0.87; P = 1.7 x 10^-43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.</p> | |
dc.format.extent | 12 | |
dc.identifier.doi | 10.1038/ncomms5999 | |
dc.identifier.uri | http://hdl.handle.net/10125/40203 | |
dc.language.iso | en-US | |
dc.publisher | Nature | |
dc.relation.uri | http://www.nature.com/ncomms/2014/140923/ncomms5999/full/ncomms5999.html | |
dc.title | Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation | |
dc.type | Article | |
dc.type.dcmi | Text |
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