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Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A and Lopez-Knowles, Elena, et al. (2016) In Nature Genetics
Abstract
We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
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  • PMID:26928228
  • WOS:000372908800009
  • Scopus:84962106221
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1546-1718
DOI
10.1038/ng.3521
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English
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6bcc5f7c-68bd-42df-8d31-f0028478a510 (old id 8856781)
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http://www.ncbi.nlm.nih.gov/pubmed/26928228?dopt=Abstract
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2016-03-15 12:01:12
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2016-11-13 04:27:44
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  abstract     = {We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.},
  author       = {Dunning, Alison M and Michailidou, Kyriaki and Kuchenbaecker, Karoline B and Thompson, Deborah and French, Juliet D and Beesley, Jonathan and Healey, Catherine S and Kar, Siddhartha and Pooley, Karen A and Lopez-Knowles, Elena and Dicks, Ed and Barrowdale, Daniel and Sinnott-Armstrong, Nicholas A and Sallari, Richard C and Hillman, Kristine M and Kaufmann, Susanne and Sivakumaran, Haran and Marjaneh, Mahdi Moradi and Lee, Jason S and Hills, Margaret and Jarosz, Monika and Drury, Suzie and Canisius, Sander and Bolla, Manjeet K and Dennis, Joe and Wang, Qin and Hopper, John L and Southey, Melissa C and Broeks, Annegien and Schmidt, Marjanka K and Lophatananon, Artitaya and Muir, Kenneth and Beckmann, Matthias W and Fasching, Peter A and Dos Santos Silva, Graciela and Peto, Julian and Sawyer, Elinor J and Tomlinson, Ian and Burwinkel, Barbara and Marme, Frederik and Guénel, Pascal and Truong, Thérèse and Bojesen, Stig E and Flyger, Henrik and González-Neira, Anna and 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Pharoah, Paul D P and Simard, Jacques and Hall, Per and García-Closas, Montserrat and Vachon, Celine and Chenevix-Trench, Georgia and Antoniou, Antonis C and Easton, Douglas F and Edwards, Stacey L},
  issn         = {1546-1718},
  language     = {eng},
  month        = {02},
  publisher    = {ARRAY(0xaf25520)},
  series       = {Nature Genetics},
  title        = {Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.},
  url          = {http://dx.doi.org/10.1038/ng.3521},
  year         = {2016},
}