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Title: Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
Authors: Kar SP,  Beesley J,  Amin Al Olama A,  Michailidou K,  Tyrer J,  Kote-Jarai Z,  Lawrenson K,  Lindstrom S,  Ramus SJ,  Thompson DJ,  ABCTB Investigators,  Kibel AS,  Dansonka-Mieszkowska A,  Michael A,  Dieffenbach AK,  Gentry-Maharaj A,  Whittemore AS,  Wolk A,  Monteiro A,  Peixoto A,  Kierzek A,  Cox A,  Rudolph A,  Gonzalez-Neira A,  Wu AH,  Lindblom A,  Swerdlow A,  AOCS Study Group & Australian Cancer Study (Ovarian Cancer),  APCB BioResource,  Ziogas A,  Ekici AB,  Burwinkel B,  Karlan BY,  Nordestgaard BG,  Blomqvist C,  Phelan C,  McLean C,  Pearce CL,  Vachon C,  Cybulski C,  Slavov C,  Stegmaier C,  Maier C,  Ambrosone CB,  Høgdall CK,  Teerlink CC,  Kang D,  Tessier DC,  Schaid DJ,  Stram DO,  Cramer DW,  Neal DE,  Eccles D,  Flesch-Janys D,  Edwards DR,  Wokozorczyk D,  Levine DA,  Yannoukakos D,  Sawyer EJ,  Bandera EV,  Poole EM,  Goode EL,  Khusnutdinova E,  Høgdall E,  Song F,  Bruinsma F,  Heitz F,  Modugno F,  Hamdy FC,  Wiklund F,  Giles GG,  Olsson H,  Wildiers H,  Ulmer HU,  Pandha H,  Risch HA,  Darabi H,  Salvesen HB,  Nevanlinna H,  Gronberg H,  Brenner H,  Brauch H,  Anton-Culver H,  Song H,  Lim HY,  McNeish I,  Campbell I,  Vergote I,  Gronwald J,  Lubiński J,  Stanford JL,  Benítez J,  Doherty JA,  Permuth JB,  Chang-Claude J,  Donovan JL,  Dennis J,  Schildkraut JM,  Schleutker J,  Hopper JL,  Kupryjanczyk J,  Park JY,  Figueroa J,  Clements JA,  Knight JA,  Peto J,  Cunningham JM,  Pow-Sang J,  Batra J,  Czene K,  Lu KH,  Herkommer K,  Khaw KT,  kConFab Investigators,  Matsuo K,  Muir K,  Offitt K,  Chen K,  Moysich KB,  Aittomäki K,  Odunsi K,  Kiemeney LA,  Massuger LF,  Fitzgerald LM,  Cook LS,  Cannon-Albright L,  Hooning MJ,  Pike MC,  Bolla MK,  Luedeke M,  Teixeira MR,  Goodman MT,  Schmidt MK,  Riggan M,  Aly M,  Rossing MA,  Beckmann MW,  Moisse M,  Sanderson M,  Southey MC,  Jones M,  Lush M,  Hildebrandt MA,  Hou MF,  Schoemaker MJ,  Garcia-Closas M,  Bogdanova N,  Rahman N,  NBCS Investigators,  Le ND,  Orr N,  Wentzensen N,  Pashayan N,  Peterlongo P,  Guénel P,  Brennan P,  Paulo P,  Webb PM,  Broberg P,  Fasching PA,  Devilee P,  Wang Q,  Cai Q,  Li Q,  Kaneva R,  Butzow R,  Kopperud RK,  Schmutzler RK,  Stephenson RA,  MacInnis RJ,  Hoover RN,  Winqvist R,  Ness R,  Milne RL,  Travis RC,  Benlloch S,  Olson SH,  McDonnell SK,  Tworoger SS,  Maia S,  Berndt S,  Lee SC,  Teo SH,  Thibodeau SN,  Bojesen SE,  Gapstur SM,  Kjær SK,  Pejovic T,  Tammela TL,  GENICA Network,  PRACTICAL consortium,  Dörk T,  Brüning T,  Wahlfors T,  Key TJ,  Edwards TL,  Menon U,  Hamann U,  Mitev V,  Kosma VM,  Setiawan VW,  Kristensen V,  Arndt V,  Vogel W,  Zheng W,  Sieh W,  Blot WJ,  Kluzniak W,  Shu XO,  Gao YT,  Schumacher F,  Freedman ML,  Berchuck A,  Dunning AM,  Simard J,  Haiman CA,  Spurdle A,  Sellers TA,  Hunter DJ,  Henderson BE,  Kraft P,  Chanock SJ,  Couch FJ,  Hall P,  Gayther SA,  Easton DF,  Chenevix-Trench G,  Eeles R,  Pharoah PD,  Lambrechts D
Journal: Cancer Discov
Date: 2016 Sep
Branches: BB, CGB, EBP, ITEB, LGS, MEB, OD, OEEB
PubMed ID: 27432226
PMC ID: PMC5010513
Abstract: UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.