Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate...

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Detalhes bibliográficos
Autores: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Cunningham, Julie M., John, Esther M., Couch, Fergus J., Bolla, Manjeet K., Casey, Graham, Margolin, Sara, Goodman, Gary, Evans, D. Gareth, Riggan, Marjorie J., Gago-Dominguez, Manuela, Jenkins, Mattias, Fostira, Florentia, Kaneva, Radka, Arnold, Susanne M., Offit, Kenneth, Ruyck, Kim De, Olsson, Håkan, Arun, Banu K., Schleutker, Johanna, Aronson, Kristan J., Caligo, Maria A., Tardón, Adonina, Edlund, Christopher K., Ingles, Sue Ann, Hsu, Li, Rosenstein, Barry S., Chenevix-Trench, Georgia, McKay, James D., Claes, Kathleen B. M., Chanock, Stephen J., Nordestgaard, Børge G., Park, Jong Y., Kupryjanczyk, Jolanta, Cadoni, Gabriella, Neal, David E., Diez, Orland, Ferris, Robert L., Stefansson, Kari, Cannon-Albright, Lisa A., Weinberg, Clarice R., McGuffog, Lesley, Raskin, Leon, Mannermaa, Arto, Kibel, Adam S., Neuhausen, Susan L., Hulick, Peter J., Shen, Hongbing, Wichmann, H-Erich, Goldberg, Mark S., Greene, Mark H., Maehle, Lovise, Yannoukakos, Drakoulis, Garber, Judy, Webb, Penelope M., Weissler, Mark C., Pejovic, Tanja, Bojesen, Stig E., Toland, Amanda E., Blomqvist, Carl, Knight, Julia A., Huntsman, David G., Dörk, Thilo, Gaudet, Mia M., Hong, Yun-Chul, Whittemore, Alice S., Torres, Diana, Hung, Rayjean J., García-Closas, Montserrat, Li, Li, Friedman, Eitan, Hillemanns, Peter, Haugen, Aage, Cruz Correa, Marcia, Wolk, Alicja, Olopade, Olufunmilayo I., Risch, Harvey A., Terry, Kathryn L., Hamdy, Freddie C., Burwinkel, Barbara, Brauch, Hiltrud, Parsons, Michael T., Tangen, Catherine M., Travis, Ruth C., Middha, Pooja, Terry, Mary Beth, Newcomb, Lisa F., Nielsen, Finn C., Ness, Andrew R., Stanford, Janet L., Kraft, Peter, Montagna, Marco, Brenton, James D., Roobol, Monique J., Thibodeau, Stephen N., Sundfeldt, Karin, Hampe, Jochen, Lubiński, Jan, Tung, Nadine, Nevanlinna, Heli, Chang-Claude, Jenny, Stone, Jennifer, Swerdlow, Anthony J., Brenner, Hermann, Wiklund, Fredrik, Bandera, Elisa V., Siegel, Erin M., Lester, Jenny, Le, Nhu D., Taylor, Jack A., Chan, Andrew T., Donovan, Jenny L., Landi, Maria Teresa, Aldrich, Melinda C., White, Emily, Stevens, Victoria L., Velez Edwards, Digna R., Goodman, Marc T., Easton, Douglas F., Dwek, Miriam, Berchuck, Andrew, deFazio, Anna, Devilee, Peter, Heitz, Florian, Hopper, John L., Hunter, David J., Peters, Ulrike, Albanes, Jeroen R., Singer, Christian F., Woll, Penella, Tajara, Eloiza H., Brunet, Joan, Christiani, David C., Weitzel, Jeffrey N., García-Sáenz, José A., Liloglou, Triantafillos, Phipps, Amanda I., Cybulski, Cezary, Li, Christopher I., Lazarus, Philip, Sawyer, Elinor J., Lane, Jacqueline M., Meindl, Alfons, Liu, Geoffrey, Grankvist, Kjell, Peters, Wilbert H. M., Goode, Ellen L., Godwin, Andrew K., Butzow, Ralf, Barkardottir, Rosa B., Bien, Stephanie A., Ulrich, Cornelia M., Brunnström, Hans, Goldgar, David E., Lee, Eunjung, Koutros, Stella, Setiawan, V. Wendy, Fletcher, Olivia, Moysich, Kirsten B., Høgdall, Estrid, Gallinger, Steven, Lacko, Martin, Chen, Chu, Beckmann, Matthias W., Elías Aguado-Barrera, Miguel, Barnes, Daniel R., Imyanitov, Evgeny N., Clements, Judith, Pandha, Hardev, Lenz, Heinz-Josef, MacInnis, Robert J., Idos, Gregory, Daly, Mary B., Anton-Culver, Hoda, Winqvist, Robert, Khusnutdinova, Elza, Muir, Kenneth, Diergaarde, Brenda, Collée, J. Margriet, Rossing, Mary Anne, Radice, Paolo, Bjørge, Line, Phelan, Catherine M., Usmani, Nawaid, Brook, Mark N., Rennert, Hedy S., Lindo, Noralane M., West, Catharine M. L., Lam, Stephan, Teare, M. Dawn, Sandler, Dale P., van Rensburg, Elizabeth J., Levine, Douglas A., Milne, Roger L., Sorensen, Karina Dalsgaard, Sutphen, Rebecca, Miller, Austin, Isaacs, Claudine, Lesse, Davor, Zheng, Wei, Campbell, Peter T., Olshan, Andrew F., Modugno, Francesmary, Ramus, Susan J., James, Paul, Cox, Angela, Caldés, Trinidad, Wang, Qin, Simard, Jacques, Schabath, Matthew B., Pasaniuc, Bogdan, Carvalho, André L., Lambrechts, Diether, Antonenkova, Natalia N., Andrew, Angeline S., Johansson, Mikael, Johansson, Mattias, Herrero, Rolando, Boccia, Stefania, Håkansson, Niclas, Kjaer, Susanne K., Berndt, Sonja I., Lejbkowicz, Flavio, Pharoah, Paul D. P., Hamilton, Robert J., Moreno Aguado, Víctor, Gruber, Stephen B., Gronberg, Henrik, Kristensen, Vessela N., Sieh, Weiva, Saxena, Richa, Bickeböller, Heike, Joshi, Amit D., Olah, Edith, Zienolddiny, Shanbeh, Vega, Ana, Gayther, Simon A., Campbell, Ian, Kühl, Tabea, Hall, Per, Rennert, Gad, Dunning, Alison M., Czene, Kamila, Stintzing, Sebastian, Osorio, Ana, Hoffmeister, Michael, Spurdle, Amanda B., Marchand, Loïc Le, Buchanan, Daniel D., Slattery, Martha L., Hamann, Ute, Caporaso, Neil E., Kelemen, Linda E., Mulligan, Anna Marie, Fortner, Renée T., Weinstein, Stephanie, Penney, Kathryn L., Mucci, Lorelei, Jakubowska, Anna, Nikitina-Zake, Liene, Loupakis, Fotios, Van Nieuwenhuysen, Els, Wu, Anna H., Pashayan, Nora, Risch, Angela, Andrulis, Irene L., Ganz, Patricia A., Maier, Christiane, Wu, Xifeng, Khaw, Kay-Tee, Southey, Melissa C., Townsend, Paul A., Thomas, Duncan, Vachon, Celine M., Eccles, Diana, Schmidt, Marjanka K., Kote-Jarai, Zsofia, Campa, Daniele, Huyghe, Jeroen R., Duell, Eric J., Claessens, Frank, May, Taymaa, Houlston, Richard, Fasching, Peter A., Kim, Jeri, Prokofyeva, Darya, Giles, Graham G., Karlan, Beth Y., Lindström, Sara, Antoniou, Antonis C., Figueiredo, Jane C., Kiemeney, Lambertus A. L. M., Eeles, Rosalind A., Kogevinas, Manolis, Bogdanova, Natalia V., Guénel, Pascal, Gronwald, Jacek, Brennan, Paul, Batra, Jyotsna, Franceschi, Silvia, Lindblom, Annika, Amos, Christopher I., Leslie, Goska, Thomassen, Mads, Haiman, Christopher A., Nussbaum, Robert L., Benlloch, Sara, Al Olama, Ali Amin, Pring, Miranda, Benitez, Javier, Ziogas, Argyrios, Cancel-Tassin, Géraldine, Price, Alkes L., Woods, Michael, Tworoger, Shelley S., Nathanson, Katherine L., Ellberg, Carolina, Teixeira, Manuel R., Saloustros, Emmanouil, Tischkowitz, Marc, Zorn, Kristin K., Plaseska-Karanfilska, Dijana, Newcomb, Polly A.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171263
Acesso em linha:https://hdl.handle.net/2445/171263
Access Level:acceso abierto
Palavra-chave:Càncer
Etiologia
Cancer
Etiology
Descrição
Resumo:Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.