Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. / Ghoussaini, Maya; Edwards, Stacey L; Michailidou, Kyriaki; Nord, Silje; Cowper-Sal Lari, Richard; Desai, Kinjal; Kar, Siddhartha; Hillman, Kristine M; Kaufmann, Susanne; Glubb, Dylan M; Beesley, Jonathan; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Guo, Qi; Schmidt, Marjanka K; Shah, Mitul; Luben, Robert; Brown, Judith; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Klevebring, Daniel; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Lambrechts, Diether; Thienpont, Bernard; Neven, Patrick; Wildiers, Hans; Broeks, Annegien; Van't Veer, Laura J; Th Rutgers, Emiel J; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Peto, Julian; Dos-Santos-Silva, Isabel; Gibson, Lorna; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Australian Ovarian Cancer Management Group.
I: Nature Communications, Bind 4, 2014, s. 1-12.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation
AU - Ghoussaini, Maya
AU - Edwards, Stacey L
AU - Michailidou, Kyriaki
AU - Nord, Silje
AU - Cowper-Sal Lari, Richard
AU - Desai, Kinjal
AU - Kar, Siddhartha
AU - Hillman, Kristine M
AU - Kaufmann, Susanne
AU - Glubb, Dylan M
AU - Beesley, Jonathan
AU - Dennis, Joe
AU - Bolla, Manjeet K
AU - Wang, Qin
AU - Dicks, Ed
AU - Guo, Qi
AU - Schmidt, Marjanka K
AU - Shah, Mitul
AU - Luben, Robert
AU - Brown, Judith
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Eriksson, Mikael
AU - Klevebring, Daniel
AU - Bojesen, Stig E
AU - Nordestgaard, Børge G
AU - Nielsen, Sune F
AU - Flyger, Henrik
AU - Lambrechts, Diether
AU - Thienpont, Bernard
AU - Neven, Patrick
AU - Wildiers, Hans
AU - Broeks, Annegien
AU - Van't Veer, Laura J
AU - Th Rutgers, Emiel J
AU - Couch, Fergus J
AU - Olson, Janet E
AU - Hallberg, Emily
AU - Vachon, Celine
AU - Chang-Claude, Jenny
AU - Rudolph, Anja
AU - Seibold, Petra
AU - Flesch-Janys, Dieter
AU - Peto, Julian
AU - Dos-Santos-Silva, Isabel
AU - Gibson, Lorna
AU - Nevanlinna, Heli
AU - Muranen, Taru A
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Australian Ovarian Cancer Management Group
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms5999
DO - 10.1038/ncomms5999
M3 - Journal article
C2 - 25248036
VL - 4
SP - 1
EP - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -
ID: 135547968