Reference details
Sawyer E, Roylance R, Petridis C, Brook MN, Nowinski S, Papouli E, Fletcher O, Pinder S, Hanby A, Kohut K, Gorman P, Caneppele M, Peto J, Dos Santos Silva I, Johnson N, Swann R, Dwek M, Perkins KA, Gillett C, Houlston R, Ross G, De Ieso P, Southey MC, Hopper JL, Provenzano E, Apicella C, Wesseling J, Cornelissen S, Keeman R, Fasching PA, Jud SM, Ekici AB, Beckmann MW, Kerin MJ, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Truong T, Laurent-Puig P, Kerbrat P, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Perez JI, Menendez P, Benitez J, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Lochmann M, Brauch H, Fischer HP, Ko YD, Network G, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Bogdanova NV, Dork T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Chenevix-Trench G, Investigators K, Lambrechts D, Weltens C, Van Limbergen E, Hatse S, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Volorio S, Giles GG, Severi G, Baglietto L, McLean CA, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labreche F, Dumont M, Kristensen V, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devillee P, Tollenaar RA, Seynaeve CM, Kriege M, Figueroa J, Chanock SJ, Sherman ME, Hooning MJ, Hollestelle A, van den Ouweland AM, van Deurzen CH, Li J, Czene K, Humphreys K, Cox A, Cross SS, Reed MW, Shah M, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Couch FJ, Hallberg E, Gonzalez-Neira A, Pita G, Alonso MR, Tessier DC, Vincent D, Bacot F, Bolla MK, Wang Q, Dennis J, Michailidou K, Dunning AM, Hall P, Easton D, Pharoah P, Schmidt MK, Tomlinson I, Garcia-Closas M (2014) Genetic predisposition to in situ and invasive lobular carcinoma of the breast. PLoS Genet 10:e1004285
ABTRACT
Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10-10; P-het for ILC vs IDC ER+ tumors = 1.8x10-4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. two="" snps="" showed="" significantly="" stronger="" associations="" for="" ilc="" than="" lcis="" (rs2981579/10q26/fgfr2,="" p-het="0.04" and="" rs889312/5q11/map3k1,="" p-het="0.03);" and="" two="" showed="" stronger="" associations="" for="" lcis="" than="" ilc="" (rs6678914/1q32/lgr6,="" p-het="0.001" and="" rs1752911/6q14,="" p-het="0.04)." in="" addition,="" seven="" of="" the="" 75="" known="" loci="" showed="" significant="" differences="" between="" er+="" tumors="" with="" idc="" and="" ilc="" histology,="" three="" of="" these="" showing="" stronger="" associations="" for="" ilc="" (rs11249433/1p11,="" rs2981579/10q26/fgfr2="" and="" rs10995190/10q21/znf365)="" and="" four="" associated="" only="" with="" idc="" (5p12/rs10941679;="" rs2588809/14q24/rad51l1,="" rs6472903/8q21="" and="" rs1550623/2q31/cdca7).="" in="" conclusion,="" we="" have="" identified="" one="" novel="" lobular="" breast="" cancer="" specific="" predisposition="" polymorphism="" at="" 7q34,="" and="" shown="" for="" the="" first="" time="" that="" common="" breast="" cancer="" polymorphisms="" predispose="" to="" lcis.="" we="" have="" shown="" that="" many="" of="" the="" er+="" breast="" cancer="" predisposition="" loci="" also="" predispose="" to="" ilc,="" although="" there="" is="" some="" heterogeneity="" between="" er+="" lobular="" and="" er+="" idc="" tumors.="" these="" data="" provide="" evidence="" for="" overlapping,="" but="" distinct="" etiological="" pathways="" within="" er+="" breast="" cancer="" between="" morphological="">
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