Genome-wide association studies identify four ER negative–specific breast cancer risk loci
Genome-wide association studies identify four ER negative–specific breast cancer risk loci
Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
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Bruning, Thomas
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Weaver, JoEllen
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Sharma, Priyanka
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Pathak, Harsh
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Tapper, Will
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Gerty, Sue
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Durcan, Lorraine
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Trichopoulos, Dimitrios
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Canzian, Federico
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Weiderpass, Elisabete
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Khaw, Kay-Tee
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Travis, Ruth
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Clavel-Chapelon, Françoise
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Kolonel, Laurence N.
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Lissowska, Jolanta
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Figueroa, Jonine D.
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Dunning, Alison M.
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Sherman, Mark E.
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Chenevix-Trench, Georgia
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Chanock, Stephen J.
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Hall, Per
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Kraft, Peter
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April 2013
Garcia-Closas, Montserrat
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Couch, Fergus J.
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Brook, Mark N.
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Orr, Nick
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Rhie, Suhn Kyong
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Feigelson, Heather S.
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Eccles, Diana
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Miron, Penelope
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Brauch, Hiltrud
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Chang-Claude, Jenny
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Nevanlinna, Heli
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Brenner, Hermann
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dos Santos Silva, Isabel
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Schneeweiss, Andreas
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Menéndez, Primitiva
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Olson, Janet E.
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Stevens, Kristen
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Balasubramanian, Sabapathy P.
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Ashworth, Alan
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Beck, Andy
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Chenevix-Trench, Georgia
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Chanock, Stephen J.
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Haiman, Christopher A.
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Kraft, Peter
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