A genome-wide "pleiotropy scan" does not identify new susceptibility Loci for estrogen receptor negative breast cancer

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Campa D, Barrdahl M, Tsilidis KK, Severi G, Diver WR, Siddiq A, Chanock S, Hoover RN, Ziegler RG, Berg CD, Buys SS, Haiman CA, Henderson BE, Schumacher FR, Le Marchand L, Flesch-Janys D, Lindstrom S, Hunter DJ, Hankinson SE, Willett WC, Kraft P, Cox DG, Khaw KT, Tjonneland A, Dossus L, Trichopoulos D, Panico S, van Gils CH, Weiderpass E, Barricarte A, Sund M, Gaudet MM, Giles G, Southey M, Baglietto L, Chang-Claude J, Kaaks R, Canzian F (2014) A genome-wide "pleiotropy scan" does not identify new susceptibility Loci for estrogen receptor negative breast cancer. PLoS One 9:e85955


Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER-positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to="" perform="" a="" secondary="" analysis="" of="" an="" er-negative="" gwas="" from="" the="" national="" cancer="" institute's="" breast="" and="" prostate="" cancer="" cohort="" consortium="" (bpc3),="" including="" 1998="" cases="" and="" 2305="" controls="" from="" prospective="" studies.="" we="" then="" tested="" the="" top="" ten="" associations="" (i.e.="" with="" the="" lowest="" p-values)="" using="" three="" additional="" populations="" with="" a="" total="" sample="" size="" of="" 3509="" er+="" cases,="" 2543="" er-="" cases="" and="" 7031="" healthy="" controls.="" none="" of="" the="" 3079="" selected="" variants="" in="" the="" bpc3="" er-gwas="" were="" significant="" at="" the="" adjusted="" threshold.="" 186="" variants="" were="" associated="" with="" er-="" breast="" cancer="" risk="" at="" a="" conventional="" threshold="" of=""><0.05, with="" p-values="" ranging="" from="" 0.049="" to="" 2.3x10(-4).="" none="" of="" the="" variants="" reached="" statistical="" significance="" in="" the="" replication="" phase.="" in="" conclusion,="" this="" study="" did="" not="" identify="" any="" novel="" susceptibility="" loci="" for="" er-breast="" cancer="" using="" a="" "pleiotropic="">

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