Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Published

Journal Article

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Full Text

Duke Authors

Cited Authors

  • Kuchenbaecker, KB; Ramus, SJ; Tyrer, J; Lee, A; Shen, HC; Beesley, J; Lawrenson, K; McGuffog, L; Healey, S; Lee, JM; Spindler, TJ; Lin, YG; Pejovic, T; Bean, Y; Li, Q; Coetzee, S; Hazelett, D; Miron, A; Southey, M; Terry, MB; Goldgar, DE; Buys, SS; Janavicius, R; Dorfling, CM; van Rensburg, EJ; Neuhausen, SL; Ding, YC; Hansen, TVO; Jønson, L; Gerdes, A-M; Ejlertsen, B; Barrowdale, D; Dennis, J; Benitez, J; Osorio, A; Garcia, MJ; Komenaka, I; Weitzel, JN; Ganschow, P; Peterlongo, P; Bernard, L; Viel, A; Bonanni, B; Peissel, B; Manoukian, S; Radice, P; Papi, L; Ottini, L; Fostira, F; Konstantopoulou, I; Garber, J; Frost, D; Perkins, J; Platte, R; Ellis, S; EMBRACE, ; Godwin, AK; Schmutzler, RK; Meindl, A; Engel, C; Sutter, C; Sinilnikova, OM; GEMO Study Collaborators, ; Damiola, F; Mazoyer, S; Stoppa-Lyonnet, D; Claes, K; De Leeneer, K; Kirk, J; Rodriguez, GC; Piedmonte, M; O'Malley, DM; de la Hoya, M; Caldes, T; Aittomäki, K; Nevanlinna, H; Collée, JM; Rookus, MA; Oosterwijk, JC; Breast Cancer Family Registry, ; Tihomirova, L; Tung, N; Hamann, U; Isaccs, C; Tischkowitz, M; Imyanitov, EN; Caligo, MA; Campbell, IG; Hogervorst, FBL; HEBON, ; Olah, E; Diez, O; Blanco, I; Brunet, J; Lazaro, C; Pujana, MA; Jakubowska, A; Gronwald, J; Lubinski, J; Sukiennicki, G; Barkardottir, RB; Plante, M; Simard, J; Soucy, P; Montagna, M; Tognazzo, S; Teixeira, MR; KConFab Investigators, ; Pankratz, VS; Wang, X; Lindor, N; Szabo, CI; Kauff, N; Vijai, J; Aghajanian, CA; Pfeiler, G; Berger, A; Singer, CF; Tea, M-K; Phelan, CM; Greene, MH; Mai, PL; Rennert, G; Mulligan, AM; Tchatchou, S; Andrulis, IL; Glendon, G; Toland, AE; Jensen, UB; Kruse, TA; Thomassen, M; Bojesen, A; Zidan, J; Friedman, E; Laitman, Y; Soller, M; Liljegren, A; Arver, B; Einbeigi, Z; Stenmark-Askmalm, M; Olopade, OI; Nussbaum, RL; Rebbeck, TR; Nathanson, KL; Domchek, SM; Lu, KH; Karlan, BY; Walsh, C; Lester, J; Australian Cancer Study (Ovarian Cancer Investigators), ; Australian Ovarian Cancer Study Group, ; Hein, A; Ekici, AB; Beckmann, MW; Fasching, PA; Lambrechts, D; Van Nieuwenhuysen, E; Vergote, I; Lambrechts, S; Dicks, E; Doherty, JA; Wicklund, KG; Rossing, MA; Rudolph, A; Chang-Claude, J; Wang-Gohrke, S; Eilber, U; Moysich, KB; Odunsi, K; Sucheston, L; Lele, S; Wilkens, LR; Goodman, MT; Thompson, PJ; Shvetsov, YB; Runnebaum, IB; Dürst, M; Hillemanns, P; Dörk, T; Antonenkova, N; Bogdanova, N; Leminen, A; Pelttari, LM; Butzow, R; Modugno, F; Kelley, JL; Edwards, RP; Ness, RB; du Bois, A; Heitz, F; Schwaab, I; Harter, P; Matsuo, K; Hosono, S; Orsulic, S; Jensen, A; Kjaer, SK; Hogdall, E; Hasmad, HN; Azmi, MAN; Teo, S-H; Woo, Y-L; Fridley, BL; Goode, EL; Cunningham, JM; Vierkant, RA; Bruinsma, F; Giles, GG; Liang, D; Hildebrandt, MAT; Wu, X; Levine, DA; Bisogna, M; Berchuck, A; Iversen, ES; Schildkraut, JM; Concannon, P; Weber, RP; Cramer, DW; Terry, KL; Poole, EM; Tworoger, SS; Bandera, EV; Orlow, I; Olson, SH; Krakstad, C; Salvesen, HB; Tangen, IL; Bjorge, L; van Altena, AM; Aben, KKH; Kiemeney, LA; Massuger, LFAG; Kellar, M; Brooks-Wilson, A; Kelemen, LE; Cook, LS; Le, ND; Cybulski, C; Yang, H; Lissowska, J; Brinton, LA; Wentzensen, N; Hogdall, C; Lundvall, L; Nedergaard, L; Baker, H; Song, H; Eccles, D; McNeish, I; Paul, J; Carty, K; Siddiqui, N; Glasspool, R; Whittemore, AS; Rothstein, JH; McGuire, V; Sieh, W; Ji, B-T; Zheng, W; Shu, X-O; Gao, Y-T; Rosen, B; Risch, HA; McLaughlin, JR; Narod, SA; Monteiro, AN; Chen, A; Lin, H-Y; Permuth-Wey, J; Sellers, TA; Tsai, Y-Y; Chen, Z; Ziogas, A; Anton-Culver, H; Gentry-Maharaj, A; Menon, U; Harrington, P; Lee, AW; Wu, AH; Pearce, CL; Coetzee, G; Pike, MC; Dansonka-Mieszkowska, A; Timorek, A; Rzepecka, IK; Kupryjanczyk, J; Freedman, M; Noushmehr, H; Easton, DF; Offit, K; Couch, FJ; Gayther, S; Pharoah, PP; Antoniou, AC; Chenevix-Trench, G; Consortium of Investigators of Modifiers of BRCA1 and BRCA2,

Published Date

  • February 2015

Published In

Volume / Issue

  • 47 / 2

Start / End Page

  • 164 - 171

PubMed ID

  • 25581431

Pubmed Central ID

  • 25581431

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.3185

Language

  • eng

Conference Location

  • United States