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

Phelan, Cm; Kuchenbaecker, Kb; Tyrer, Jp; Kar, Sp; Lawrenson, K; Winham, Sj; Dennis, J; Pirie, A; Riggan, Mj; Chornokur, G; Earp, Ma; Lyra, PC Jr; Lee, Jm; Coetzee, S; Beesley, J; Mcguffog, L; Soucy, P; Dicks, E; Lee, A; Barrowdale, D; Lecarpentier, J; Leslie, G; Aalfs, Cm; Aben, Kk; Adams, M; Adlard, J; Andrulis, Il; Anton Culver, H; Antonenkova, N; study group, AOCS .; Aravantinos, G; Arnold, N; Arun, Bk; Arver, B; Azzollini, J; Balmaña, J; Banerjee, Sn; Barjhoux, L; Barkardottir, Rb; Bean, Y; Beckmann, Mw; Beeghly Fadiel, A; Benitez, J; Bermisheva, M; Bernardini, Mq; Birrer, Mj; Bjorge, L; Black, A; Blankstein, K; Blok, Mj; Bodelon, C; Bogdanova, N; Bojesen, A; Bonanni, B; Borg, Å; Bradbury, Ar; Brenton, Jd; Brewer, C; Brinton, L; Broberg, P; Brooks Wilson, A; Bruinsma, F; Brunet, J; Buecher, B; Butzow, R; Buys, Ss; Caldes, T; Caligo, Ma; Campbell, I; Cannioto, R; Carney, Me; Cescon, T; Chan, Sb; Chang Claude, J; Chanock, S; Chen, Xq; Chiew, Ye; Chiquette, J; Chung, Wk; Claes, Kb; Conner, T; Cook, Ls; Cook, J; Cramer, Dw; Cunningham, Jm; D'Aloisio, Aa; Daly, Mb; Damiola, F; Damirovna, Sd; Dansonka Mieszkowska, A; Dao, F; Davidson, R; Defazio, A; Delnatte, C; Doheny, Kf; Diez, O; Ding, Yc; Doherty, Ja; Domchek, Sm; Dorfling, Cm; Dörk, T; Dossus, L; Duran, M; Dürst, M; Dworniczak, B; Eccles, D; Edwards, T; Eeles, R; Eilber, U; Ejlertsen, B; Ekici, Ab; Ellis, S; Elvira, M; Embrace, Study; Eng, Kh; Engel, C; Evans, Dg; Fasching, Pa; Ferguson, S; Ferrer, Sf; Flanagan, Jm; Fogarty, Zc; Fortner, Rt; Fostira, F; Foulkes, Wd; Fountzilas, G; Fridley, Bl; Friebel, Tm; Friedman, E; Frost, D; Ganz, Pa; Garber, J; García, Mj; Garcia Barberan, V; Gehrig, A; Study Collaborators, GEMO .; 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, Tv; Harrington, Pa; Harris, Hr; Hauke, J; Hebon, Study; Hein, A; Henderson, A; Hildebrandt, Ma; Hillemanns, P; Hodgson, S; Høgdall, Ck; Høgdall, E; Hogervorst, Fb; 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; Jakubowska, A; James, P; Janavicius, R; Jernetz, M; Jensen, A; Jensen, Ub; John, Em; Johnatty, S; Jones, Me; Kannisto, P; Karlan, By; Karnezis, A; Kast, K; Kconfab, Investigators; Kennedy, Cj; Khusnutdinova, E; Kiemeney, La; Kiiski, Ji; Kim, Sw; Kjaer, Sk; Köbel, M; Kopperud, Rk; Kruse, Ta; Kupryjanczyk, J; Kwong, A; Laitman, Y; Lambrechts, D; Larrañaga, N; Larson, Mc; Lazaro, C; Nd, Le; Le Marchand, L; Lee, Jw; Lele, Sb; Leminen, A; Leroux, D; Lester, J; Lesueur, F; Levine, Da; Liang, D; Liebrich, C; Lilyquist, J; Lipworth, L; Lissowska, J; Kh, Lu; Lubinński, J; Luccarini, C; Lundvall, L; Mai, Pl; Mendoza Fandiño, G; Manoukian, S; Massuger, Lf; May, T; Mazoyer, S; Mcalpine, Jn; Mcguire, V; Mclaughlin, Jr; Mcneish, I; Meijers Heijboer, H; Meindl, A; Menon, U; Mensenkamp, Ar; Merritt, Ma; Milne, Rl; Mitchell, G; Modugno, F; Moes Sosnowska, J; Moffitt, M; Montagna, M; Moysich, Kb; Mulligan, Am; 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; Onland Moret, Nc; study group, OPAL .; Orr, N; Orsulic, S; Osorio, A; Palli, D; Papi, Laura; Park Simon, Tw; Paul, J; Pearce, Cl; Pedersen, Is; Peeters, Ph; Peissel, B; Peixoto, A; Pejovic, T; Pelttari, Lm; 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; Rennert, G; Rhiem, K; 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; Schoemaker, Mj; Senter, L; Setiawan, Vw; Severi, G; Sharma, P; Shelford, T; Siddiqui, N; Side, Le; Sieh, W; Singer, Cf; Sobol, H; Song, H; Southey, Mc; Spurdle, Ab; Stadler, Z; Steinemann, D; Stoppa Lyonnet, D; Sucheston Campbell, Le; Sukiennicki, G; Sutphen, R; Sutter, C; Swerdlow, Aj; Szabo, Ci; Szafron, L; Tan, Yy; Taylor, Ja; Tea, Mk; Teixeira, Mr; Teo, Sh; Terry, Kl; Thompson, Pj; Thomsen, Lc; Thull, Dl; Tihomirova, L; Tinker, Av; Tischkowitz, M; Tognazzo, S; Toland, Ae; Tone, A; Trabert, B; Travis, Rc; Trichopoulou, A; Tung, N; Tworoger, Ss; van Altena, Am; Van Den Berg, D; van der Hout, Ah; van der Luijt, Rb; Van Heetvelde, M; Van Nieuwenhuysen, E; van Rensburg, Ej; Vanderstichele, A; Varon Mateeva, R; Vega, A; Edwards, Dv; Vergote, I; Vierkant, Ra; Vijai, J; Vratimos, A; Walker, L; Walsh, C; Wand, D; Wang Gohrke, S; Wappenschmidt, B; Webb, Pm; Weinberg, Cr; Weitzel, Jn; Wentzensen, N; Whittemore, As; Wijnen, Jt; Wilkens, Lr; Wolk, A; Woo, M; Wu, X; Ah, Wu; Yang, H; Yannoukakos, D; Ziogas, A; Zorn, Kk; Narod, Sa; Easton, Df; Amos, Ci; Schildkraut, Jm; Ramus, Sj; Ottini, L; Goodman, Mt; Park, Sk; Kelemen, Le; Risch, Ha; Thomassen, M; Offit, K; Simard, J; Schmutzler, Rk; Hazelett, D; Monteiro, An; Couch, Fj; Berchuck, A; Chenevix Trench, G; Goode, El; Sellers, Ta; Gayther, Sa; Antoniou, Ac; Pharoah, P. d.

doi:doi: 10.1038/ng.3826

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.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer / Phelan, Cm; Kuchenbaecker, Kb; Tyrer, Jp; Kar, Sp; Lawrenson, K; Winham, Sj; Dennis, J; Pirie, A; Riggan, Mj; Chornokur, G; Earp, Ma; Lyra, PC Jr; Lee, Jm; Coetzee, S; Beesley, J; Mcguffog, L; Soucy, P; Dicks, E; Lee, A; Barrowdale, D; Lecarpentier, J; Leslie, G; Aalfs, Cm; Aben, Kk; Adams, M; Adlard, J; Andrulis, Il; Anton-Culver, H; Antonenkova, N; study group, AOCS .; Aravantinos, G; Arnold, N; Arun, Bk; Arver, B; Azzollini, J; Balmaña, J; Banerjee, Sn; Barjhoux, L; Barkardottir, Rb; Bean, Y; Beckmann, Mw; Beeghly-Fadiel, A; Benitez, J; Bermisheva, M; Bernardini, Mq; Birrer, Mj; Bjorge, L; Black, A; Blankstein, K; Blok, Mj; Bodelon, C; Bogdanova, N; Bojesen, A; Bonanni, B; Borg, Å; Bradbury, Ar; Brenton, Jd; Brewer, C; Brinton, L; Broberg, P; Brooks-Wilson, A; Bruinsma, F; Brunet, J; Buecher, B; Butzow, R; Buys, Ss; Caldes, T; Caligo, Ma; Campbell, I; Cannioto, R; Carney, Me; Cescon, T; Chan, Sb; Chang-Claude, J; Chanock, S; Chen, Xq; Chiew, Ye; Chiquette, J; Chung, Wk; Claes, Kb; Conner, T; Cook, Ls; Cook, J; Cramer, Dw; Cunningham, Jm; D'Aloisio, Aa; Daly, Mb; Damiola, F; Damirovna, Sd; Dansonka-Mieszkowska, A; Dao, F; Davidson, R; Defazio, A; Delnatte, C; Doheny, Kf; Diez, O; Ding, Yc; Doherty, Ja; Domchek, Sm; Dorfling, Cm; Dörk, T; Dossus, L; Duran, M; Dürst, M; Dworniczak, B; Eccles, D; Edwards, T; Eeles, R; Eilber, U; Ejlertsen, B; Ekici, Ab; Ellis, S; Elvira, M; Embrace, Study.; Eng, Kh; Engel, C; Evans, Dg; Fasching, Pa; Ferguson, S; Ferrer, Sf; Flanagan, Jm; Fogarty, Zc; Fortner, Rt; Fostira, F; Foulkes, Wd; Fountzilas, G; Fridley, Bl; Friebel, Tm; Friedman, E; Frost, D; Ganz, Pa; Garber, J; García, Mj; Garcia-Barberan, V; Gehrig, A; Study Collaborators, GEMO .; 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, Tv; Harrington, Pa; Harris, Hr; Hauke, J; Hebon, Study.; Hein, A; Henderson, A; Hildebrandt, Ma; Hillemanns, P; Hodgson, S; Høgdall, Ck; Høgdall, E; Hogervorst, Fb; 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; Jakubowska, A; James, P; Janavicius, R; Jernetz, M; Jensen, A; Jensen, Ub; John, Em; Johnatty, S; Jones, Me; Kannisto, P; Karlan, By; Karnezis, A; Kast, K; Kconfab, Investigators.; Kennedy, Cj; Khusnutdinova, E; Kiemeney, La; Kiiski, Ji; Kim, Sw; Kjaer, Sk; Köbel, M; Kopperud, Rk; Kruse, Ta; Kupryjanczyk, J; Kwong, A; Laitman, Y; Lambrechts, D; Larrañaga, N; Larson, Mc; Lazaro, C; Le, Nd; Le Marchand, L; Lee, Jw; Lele, Sb; Leminen, A; Leroux, D; Lester, J; Lesueur, F; Levine, Da; Liang, D; Liebrich, C; Lilyquist, J; Lipworth, L; Lissowska, J; Lu, Kh; Lubinński, J; Luccarini, C; Lundvall, L; Mai, Pl; Mendoza-Fandiño, G; Manoukian, S; Massuger, Lf; May, T; Mazoyer, S; Mcalpine, Jn; Mcguire, V; Mclaughlin, Jr; Mcneish, I; Meijers-Heijboer, H; Meindl, A; Menon, U; Mensenkamp, Ar; Merritt, Ma; Milne, Rl; Mitchell, G; Modugno, F; Moes-Sosnowska, J; Moffitt, M; Montagna, M; Moysich, Kb; Mulligan, Am; 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; Onland-Moret, Nc; study group, OPAL .; Orr, N; Orsulic, S; Osorio, A; Palli, D; Papi, L; Park-Simon, Tw; Paul, J; Pearce, Cl; Pedersen, Is; Peeters, Ph; Peissel, B; Peixoto, A; Pejovic, T; Pelttari, Lm; 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; Rennert, G; Rhiem, K; 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; Schoemaker, Mj; Senter, L; Setiawan, Vw; Severi, G; Sharma, P; Shelford, T; Siddiqui, N; Side, Le; Sieh, W; Singer, Cf; Sobol, H; Song, H; Southey, Mc; Spurdle, Ab; Stadler, Z; Steinemann, D; Stoppa-Lyonnet, D; Sucheston-Campbell, Le; Sukiennicki, G; Sutphen, R; Sutter, C; Swerdlow, Aj; Szabo, Ci; Szafron, L; Tan, Yy; Taylor, Ja; Tea, Mk; Teixeira, Mr; Teo, Sh; Terry, Kl; Thompson, Pj; Thomsen, Lc; Thull, Dl; Tihomirova, L; Tinker, Av; Tischkowitz, M; Tognazzo, S; Toland, Ae; Tone, A; Trabert, B; Travis, Rc; Trichopoulou, A; Tung, N; Tworoger, Ss; van Altena, Am; Van Den Berg, D; van der Hout, Ah; van der Luijt, Rb; Van Heetvelde, M; Van Nieuwenhuysen, E; van Rensburg, Ej; Vanderstichele, A; Varon-Mateeva, R; Vega, A; Edwards, Dv; Vergote, I; Vierkant, Ra; Vijai, J; Vratimos, A; Walker, L; Walsh, C; Wand, D; Wang-Gohrke, S; Wappenschmidt, B; Webb, Pm; Weinberg, Cr; Weitzel, Jn; Wentzensen, N; Whittemore, As; Wijnen, Jt; Wilkens, Lr; Wolk, A; Woo, M; Wu, X; Wu, Ah; Yang, H; Yannoukakos, D; Ziogas, A; Zorn, Kk; Narod, Sa; Easton, Df; Amos, Ci; Schildkraut, Jm; Ramus, Sj; Ottini, L; Goodman, Mt; Park, Sk; Kelemen, Le; Risch, Ha; Thomassen, M; Offit, K; Simard, J; Schmutzler, Rk; Hazelett, D; Monteiro, An; Couch, Fj; Berchuck, A; Chenevix-Trench, G; Goode, El; Sellers, Ta; Gayther, Sa; Antoniou, Ac; Pharoah, Pd.. - In: NATURE GENETICS. - ISSN 1061-4036. - ELETTRONICO. - Epub:(2017), pp. 680-691. [doi: 10.1038/ng.3826]