Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

Abstract:

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Authors:

CM Phelan, KB Kuchenbaecker, JP Tyrer, SP Kar, K Lawrenson, SJ Winham, J Dennis, A Pirie, MJ Riggan, G Chornokur, MA Earp, PC Lyra, JM Lee, S Coetzee, J Beesley, L McGuffog, P Soucy, E Dicks, A Lee, D Barrowdale, J Lecarpentier, G Leslie, CM Aalfs, KKH Aben, M Adams, J Adlard, IL Andrulis, H Anton-Culver, N Antonenkova, AOCS study group, G Aravantinos, N Arnold, BK Arun, B Arver, J Azzollini, J Balmaña, SN Banerjee, L Barjhoux, RB Barkardottir, Y Bean, MW Beckmann, A Beeghly-Fadiel, J Benitez, M Bermisheva, MQ Bernardini, MJ Birrer, L Bjorge, A Black, K Blankstein, MJ Blok, C Bodelon, N Bogdanova, A Bojesen, B Bonanni, Å Borg, AR Bradbury, JD Brenton, C Brewer, L Brinton, P Broberg, A Brooks-Wilson, F Bruinsma, J Brunet, B Buecher, R Butzow, SS Buys, T Caldes, MA Caligo, I Campbell, R Cannioto, ME Carney, T Cescon, SB Chan, J Chang-Claude, S Chanock, XQ Chen, Y-E Chiew, J Chiquette, WK Chung, KBM Claes, T Conner, LS Cook, J Cook, DW Cramer, JM Cunningham, AA D'Aloisio, MB Daly, F Damiola, SD Damirovna, A Dansonka-Mieszkowska, F Dao, R Davidson, A DeFazio, C Delnatte, KF Doheny, O Diez, YC Ding, JA Doherty, SM Domchek, CM Dorfling, T Dörk, L Dossus, M Duran, M Dürst, B Dworniczak, D Eccles, T Edwards, R Eeles, U Eilber, B Ejlertsen, AB Ekici, S Ellis, M Elvira, EMBRACE Study, KH Eng, C Engel, DG Evans, PA Fasching, S Ferguson, SF Ferrer, JM Flanagan, ZC Fogarty, RT Fortner, F Fostira, WD Foulkes, G Fountzilas, BL Fridley, TM Friebel, E Friedman, D Frost, PA Ganz, J Garber, MJ García, V Garcia-Barberan, A Gehrig, GEMO Study Collaborators, A Gentry-Maharaj, A-M Gerdes, GG Giles, R Glasspool, G Glendon, AK Godwin, DE Goldgar, T Goranova, M Gore, MH Greene, J Gronwald, S Gruber, E Hahnen, CA Haiman, N Håkansson, U Hamann, TVO Hansen, PA Harrington, HR Harris, J Hauke, HEBON Study, A Hein, A Henderson, MAT Hildebrandt, P Hillemanns, S Hodgson, CK Høgdall, E Høgdall, FBL Hogervorst, H Holland, MJ Hooning, K Hosking, R-Y Huang, PJ Hulick, J Hung, DJ Hunter, DG Huntsman, T Huzarski, EN Imyanitov, C Isaacs, ES Iversen, L Izatt, A Izquierdo, A Jakubowska, P James, R Janavicius, M Jernetz, A Jensen, UB Jensen, EM John, S Johnatty, ME Jones, P Kannisto, BY Karlan, A Karnezis, K Kast, KConFab Investigators, CJ Kennedy, E Khusnutdinova, LA Kiemeney, JI Kiiski, S-W Kim, SK Kjaer, M Köbel, RK Kopperud, TA Kruse, J Kupryjanczyk, A Kwong, Y Laitman, D Lambrechts, N Larrañaga, MC Larson, C Lazaro, ND Le, L Le Marchand, JW Lee, SB Lele, A Leminen, D Leroux, J Lester, F Lesueur, DA Levine, D Liang, C Liebrich, J Lilyquist, L Lipworth, J Lissowska, KH Lu, J Lubinński, C Luccarini, L Lundvall, PL Mai, G Mendoza-Fandiño, S Manoukian, LFAG Massuger, T May, S Mazoyer, JN McAlpine, V McGuire, JR McLaughlin, I McNeish, H Meijers-Heijboer, A Meindl, U Menon, AR Mensenkamp, MA Merritt, RL Milne, G Mitchell, F Modugno, J Moes-Sosnowska, M Moffitt, M Montagna, KB Moysich, AM Mulligan, J Musinsky, KL Nathanson, L Nedergaard, RB Ness, SL Neuhausen, H Nevanlinna, D Niederacher, RL Nussbaum, K Odunsi, E Olah, OI Olopade, H Olsson, C Olswold, DM O'Malley, K-R Ong, NC Onland-Moret, OPAL study group, N Orr, S Orsulic, A Osorio, D Palli, L Papi, T-W Park-Simon, J Paul, CL Pearce, IS Pedersen, PHM Peeters, B Peissel, A Peixoto, T Pejovic, LM Pelttari, JB Permuth, P Peterlongo, L Pezzani, G Pfeiler, K-A Phillips, M Piedmonte, MC Pike, AM Piskorz, SR Poblete, T Pocza, EM Poole, B Poppe, ME Porteous, F Prieur, D Prokofyeva, E Pugh, MA Pujana, P Pujol, P Radice, J Rantala, C Rappaport-Fuerhauser, G Rennert, K Rhiem, P Rice, A Richardson, M Robson, GC Rodriguez, C Rodríguez-Antona, J Romm, MA Rookus, MA Rossing, JH Rothstein, A Rudolph, IB Runnebaum, HB Salvesen, DP Sandler, MJ Schoemaker, L Senter, VW Setiawan, G Severi, P Sharma, T Shelford, N Siddiqui, LE Side, W Sieh, CF Singer, H Sobol, H Song, MC Southey, AB Spurdle, Z Stadler, D Steinemann, D Stoppa-Lyonnet, LE Sucheston-Campbell, G Sukiennicki, R Sutphen, C Sutter, AJ Swerdlow, CI Szabo, L Szafron, YY Tan, JA Taylor, M-K Tea, MR Teixeira, S-H Teo, KL Terry, PJ Thompson, LCV Thomsen, DL Thull, L Tihomirova, AV Tinker, M Tischkowitz, S Tognazzo, AE Toland, A Tone, B Trabert, RC Travis, A Trichopoulou, N Tung, SS Tworoger, AM van Altena, D Van Den Berg, AH van der Hout, RB van der Luijt, M Van Heetvelde, E Van Nieuwenhuysen, EJ van Rensburg, A Vanderstichele, R Varon-Mateeva, A Vega, DV Edwards, I Vergote, RA Vierkant, J Vijai, A Vratimos, L Walker, C Walsh, D Wand, S Wang-Gohrke, B Wappenschmidt, PM Webb, CR Weinberg, JN Weitzel, N Wentzensen, AS Whittemore, JT Wijnen, LR Wilkens, A Wolk, M Woo, X Wu, AH Wu, H Yang, D Yannoukakos, A Ziogas, KK Zorn, SA Narod, DF Easton, CI Amos, JM Schildkraut, SJ Ramus, L Ottini, MT Goodman, SK Park, LE Kelemen, HA Risch, M Thomassen, K Offit, J Simard, RK Schmutzler, D Hazelett, AN Monteiro, FJ Couch, A Berchuck, G Chenevix-Trench, EL Goode, TA Sellers, SA Gayther, AC Antoniou, PDP Pharoah

Journal:

Nat Genet

Citation info:

49(5):680-691

Publication date:

1st May 2017

Full text

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