Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.8...

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Authors: Wolpin, Brian M., Rizzato, Cosmeri, Kraft, Peter, Kooperberg, Charles, Petersen, Gloria M., Wang, Zhaoming, Arslan, Alan A., Beane Freeman, Laura, Bracci, Paige M., Buring, Julie E., Canzian, Federico, Albanes, Demetrius, Andreotti, Gabriella, Bugert, Peter, Austin, Melissa A., Barfield, Richard T., Basso, Daniela, Capurso, Gabriele, Berndt, Sonja I., Brotzman, Michelle, Büchler, Markus W., Costello, Eithne, Bueno de Mesquita, H. Bas, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Chung, Charles C., Giovannucci, Edward L., Cotterchio, Michelle, Elena, Joanne W., Hassan, Manal, Funel, Niccola, Gaziano, J. Michael M., Giese, Nathalia A., Hu, Nan, Goggins, Michael, Gorman, Megan J, Gross, Myron D., Jenab, Mazda, Haiman, Christopher A., Helzlsouer, Kathy J., Henderson, Brian E., Holly, Elizabeth A., Hunter, David J., Kogevinas, Manolis, Innocenti, Federico, Kaaks, Rudolf, Landi, Maria Teresa, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Mannisto, Satu, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., Oberg, Ann L., LaCroix, Andrea, Landi, Stefano, Marchand, Loïc Le, Mambrini, Andrea, Peters, Ulrike, Milne, Roger L., Nakamura, Yusuke, Owzar, Kouros, Rothman, Nathaniel, Patel, Alpa V., Peeters, Petra H. M., Pezzilli, Raffaele, Tjønneland, Anne, Piepoli, Ada, Porta, Miquel, 1957-, Real, Francisco X., Taylor, Philip R., Riboli, Elio, Scarpa, Aldo, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Theodoropoulos, George E., Yu, Herbert, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulos, Dimitrios, Hoover, Robert N., Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Stolzenberg-Solomon, Rachael Z., Wu, Chen, Yu, Kai, Zeleniuch-Jacquotte, Anne, Duell, Eric J., Hartge, Patricia, Fuchs, Charles S., Chanock, Stephen J., Amundadottir, Laufey, Kolonel, Laurence N., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Olson, Sara H., Goodman, Phyllis J., Jacobs, Eric J., Kamineni, Aruna, White, Emily, Klein, Alison P., Kulke, Matthew H., Li, Donghui, Malats, Núria, Risch, Harvey A., Sesso, Howard D., Visvanathan, Kala, Zheng, Wei, Boutron-Ruault, Marie-Christine, Abnet, Christian C.
Format: article
Status:Versión aceptada para publicación
Publication Date:2014
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/126331
Online Access:https://hdl.handle.net/2445/126331
Access Level:Open access
Keyword:Genòmica
Càncer de pàncrees
Genomics
Pancreas cancer
Description
Summary:We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

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