Does gadolinium-based angiography protect against contrast-induced nephropathy?: A systematic review of the literature

We evaluated the incidence of contrast-induced nephropathy (CIN) in patients exposed to gadolinium for diagnostic or therapeutic procedures. Background: CIN with iodinated contrast agents is a leading cause of acute renal failure. Gadolinium is often used as an alternative to iodinated contrast in patients at increased risk of CIN. The safety of gadolinium in patients at increased risk of CIN has not been established. Methods and Results: The authors performed a systematic review by searching MEDLINE, ISI Web of Knowledge, Current Contents, Embase, and the Cochrane Central Register of Controlled Trials to identify relevant studies evaluating gadolinium and its associated incidence of CIN. They identified 17 studies that reported both favorable and negative results with regard to the association of gadolinium and CIN. The differences in the results appeared to be dose related. When gadolinium was used in doses of 0.4 mmol/kg or higher, there appeared to be an increased incidence of ARF particularly in patients with preexisting renal insufficiency. Conclusions: Although the evidence base is limited, gadolinium does not appear to be safer than iodinated contrast in patients at risk of CIN. Given the lack of randomized data to support its safety, gadolinium in lieu of iso-osmolar iodinated contrast cannot be advocated in patients at high risk of contrast nephropathy. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58087/1/21459_ftp.pd

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

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 × 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

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

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 × 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

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999