Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic C...

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Autores: Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Chen, Fei, Neoptolemos, John P., Shu, Xiao-Ou, Oberg, Ann L., Severi, Gianluca, Olson, Sara H., Pasquali, Claudio, Patel, Alpa V., Soucek, Pavel, Talar-Wojnarowska, Renata, Pezzilli, Raffaele, Eeden, Stephen K. van den, Porta, Miquel, 1957-, Rothman, Nathaniel, Scelo, Ghislaine, Vodicka, Pavel, Sesso, Howard D., Sund, Malin, Silverman, Debra T., Wentzensen, Nicolas, Smith, Jill P., Tavano, Francesca, Zeleniuch-Jacquotte, Anne, Thornquist, Mark D., Arslan, Alan A., Tobias, Geoffrey S., Vashist, Yogesh, Chanock, Stephen J., Visvanathan, Kala, Wactawski-Wende, Jean, Wang, Zhaoming, Amundadottir, Laufey, White, Emily, Yu, Herbert, Berndt, Sonja I., Yu, Kai, Zheng, Wei, Kraft, Peter, Borgida, Ayelet, Li, Donghui, Obazee, Ofure, Andreotti, Gabriella, Brennan, Paul, Petersen, Gloria M., Babic, Ana, Duell, Eric J., Bamlet, William R., Campa, Daniele, Beane Freeman, Laura, Blackford, Amanda, Chung, Charles C., Borges, Michael, Bracci, Paige M., Albanes, Demetrius, Brais, Lauren, Brenner, Hermann, Bueno de Mesquita, H. Bas, Funel, Niccola, Buring, Julie E., Capurso, Gabriele, Cavestro, Giulia Martina, Gazouli, Maria, Chaffee, Kari G., Dijk, Frederike, Cleary, Sean, Goggins, Michael, Cotterchio, Michelle, Zhong, Jun, Hartge, Patricia, Foretova, Lenka, Haiman, Christopher A., Fuchs, Charles S., Gallinger, Steven, Gaziano, J. Michael M., Herman, Joseph, Giles, Graham G., Giovannucci, Edward L., Hoover, Robert N., Goodman, Gary E., Goodman, Phyllis J., Kaaks, Rudolf, Hackert, Thilo, Hung, Rayjean J., Hasan, Manal, Kogevinas, Manolis, Hegyi, Peter, Helzlsouer, Kathy J., Holcátová, Ivana, Kupcinskas, Juozas, Holly, Elizabeth A., Jacobs, Eric J., Lee, I. Min, Jamroziak, Krzysztof, Lawlor, Rita T., Janout, Vladimir, Khaw, Kay-Tee, Klein, Eric A., Mohelníková Duchoňová, Beatrice, Kooperberg, Charles, Milne, Roger L., Kulke, Matthew H., Kurtz, Robert J., Laheru, Daniel, Orlow, Irene, Landi, Stefano, Mambrini, Andrea, LeMarchand, Loic, Peters, Ulrike, Lu, Lingeng, Malats, Núria, Mannisto, Satu, Real, Francisco X., Neale, Rachel E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/121082
Acceso en línea:https://hdl.handle.net/2445/121082
Access Level:acceso abierto
Palabra clave:Càncer
Càncer de pàncrees
Cancer
Pancreas cancer
Descripción
Sumario:In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10−8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10−14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10−10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10−8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10−8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

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