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

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.

Full Text

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

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-15-1227

Language

  • eng

Conference Location

  • United States