Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

Published

Journal Article

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.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.

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Duke Authors

Cited 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, DRV; 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, H-U; Pandha, H; Risch, HA; Darabi, H; Salvesen, HB; Nevanlinna, H; Gronberg, H; Brenner, H; Brauch, H; Anton-Culver, H; Song, H; Lim, H-Y; McNeish, I; Campbell, I; Vergote, I; Gronwald, J; LubiƄski, 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, K-T; kConFab Investigators, ; Matsuo, K; Muir, K; Offitt, K; Chen, K; Moysich, KB; Aittomäki, K; Odunsi, K; Kiemeney, LA; Massuger, LFAG; 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, MAT; Hou, M-F; 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, S-H; Thibodeau, SN; Bojesen, SE; Gapstur, SM; Kjær, SK; Pejovic, T; Tammela, TLJ; GENICA Network, ; PRACTICAL consortium, ; Dörk, T; Brüning, T; Wahlfors, T; Key, TJ; Edwards, TL; Menon, U; Hamann, U; Mitev, V; Kosma, V-M; Setiawan, VW; Kristensen, V; Arndt, V; Vogel, W; Zheng, W; Sieh, W; Blot, WJ; Kluzniak, W; Shu, X-O; Gao, Y-T; 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, PDP; Lambrechts, D

Published Date

  • September 2016

Published In

Volume / Issue

  • 6 / 9

Start / End Page

  • 1052 - 1067

PubMed ID

  • 27432226

Pubmed Central ID

  • 27432226

Electronic International Standard Serial Number (EISSN)

  • 2159-8290

International Standard Serial Number (ISSN)

  • 2159-8274

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-15-1227

Language

  • eng