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

Phelan CM, Kuchenbaecker KB, Tyrer JP, Siddhartha Kar, Kate Lawrenson, Stacey J. Winham, Dennis J, Pirie A, Riggan MJ, Chornokur G, Earp MA, Lyra PC Jr, Lee JM, Simon G. Coetzee, Beesley J, McGuffog L, Soucy P, Dicks E, Lee A, Barrowdale D, Lecarpentier J, Leslie G, Aalfs CM, Katja K.H. 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Ekici, Ellis S, Elvira M, Eng KH, Engel C, Evans DG, Fasching PA, Ferguson S, Ferrer SF, Flanagan JM, Fogarty Z, Renée T. Fortner, Fostira F, Foulkes WD, Fountzilas G, Fridley BL, Friebel TM, Friedman E, Frost D, Ganz PA, Garber J, María J. García, Garcia-Barberan V, Gehrig A, Gentry-Maharaj A, Gerdes AM, Giles GG, Glasspool R, Glendon G, Godwin AK, Goldgar DE, Goranova T, Gore M, Greene MH, Gronwald J, Gruber S, Hahnen E, Haiman CA, Håkansson N, Hamann U, Hansen TVO, Harrington PA, Harris HR, Hauke J, Alexander Hein, Henderson A, Hildebrandt MAT, Peter Hillemanns, Hodgson S, Høgdall CK, Høgdall E, Hogervorst FBL, Holland H, Hooning MJ, Hosking K, Huang RY, Hulick PJ, Hung J, Hunter DJ, Huntsman DG, Huzarski T, Imyanitov EN, Isaacs C, Iversen ES, Izatt L, Izquierdo A, Anna Jakubowska, James P, Janavicius R, Jernetz M, Jensen A, Jensen UB, Esther M. John, Johnatty S, Michael E. Jones, Kannisto P, Karlan BY, Karnezis A, Kast K, Kennedy CJ, Khusnutdinova E, Lambertus A. Kiemeney, Kiiski JI, Kim SW, Kjaer SK, Martin Köbel, Kopperud RK, Kruse TA, Jolanta Kupryjańczyk, Ava Kwong, Laitman Y, Diether Lambrechts, Larrañaga N, Larson MC, Lazaro C, Le ND, Le Marchand L, Lee JW, Lele SB, Leminen A, Leroux D, Lester J, Lesueur F, Douglas A. Levine, Dong Liang, Liebrich C, Lilyquist J, Lipworth L, Jolanta Lissowska, Lu KH, Lubinński J, Luccarini C, Lundvall L, Mai PL, Mendoza-Fandiño G, Manoukian S, Massuger LFAG, May T, Mazoyer S, McAlpine JN, McGuire V, McLaughlin JR, Iain A. McNeish, Meijers-Heijboer H, Meindl A, Usha Menon, Mensenkamp AR, Melissa A. Merritt, Milne RL, Mitchell G, Modugno F, Moes-Sosnowska J, Moffitt M, Montagna M, Moysich KB, Anna Marie Mulligan, Musinsky J, Nathanson KL, Nedergaard L, Ness RB, Neuhausen SL, Nevanlinna H, Niederacher D, Nussbaum RL, Odunsi K, Olah E, Olopade OI, Olsson H, Olswold C, O'Malley DM, Ong KR, N. Charlotte Onland‐Moret, Orr N, Orsulic S, Osorio A, Palli D, Papi L, Park-Simon TW, Paul J, Pearce CL, Pedersen IS, Peeters PHM, Peissel B, Peixoto A, Pejovic T, Liisa M. Pelttari, Permuth JB, Peterlongo P, Pezzani L, Pfeiler G, Phillips KA, Piedmonte M, Pike MC, Piskorz AM, Poblete SR, Pocza T, Poole EM, Poppe B, Porteous ME, Prieur F, Prokofyeva D, Pugh E, Pujana MA, Pujol P, Radice P, Rantala J, Rappaport-Fuerhauser C, Gad Rennert, Kerstin Rhiem, Rice P, Richardson A, Robson M, Rodriguez GC, Rodríguez-Antona C, Romm J, Rookus MA, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Salvesen HB, Sandler DP, Minouk J. Schoemaker, Senter L, Veronica Wendy Setiawan, Severi G, Priyanka Sharma, Shelford T, Siddiqui N, Side LE, Weiva Sieh, Singer CF, Sobol H, Song H, Melissa C. Southey, Spurdle AB, Stadler Z, Steinemann D, Stoppa-Lyonnet D, Sucheston-Campbell LE, Sukiennicki G, Sutphen R, Sutter C, Anthony J. Swerdlow, Szabo CI, Lukasz M. Szafron, Tan YY, Taylor JA, Tea MK, Manuel R. 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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.

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