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

We performed a multistage genome-wide association study (GWAS) 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] =...

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Detalles Bibliográficos
Autores principales: 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, Canzian, Federico, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Goodman, Phyllis J., Jacobs, Eric J., Kamineni, Aruna, Klein, Alison P., Kolonel, Laurence N., Kulke, Matthew H., Li, Donghui, Malats, Núria, Olson, Sara H., Risch, Harvey A., Sesso, Howard D., Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C., Albanes, Demetrius, Andreotti, Gabriella, Austin, Melissa A., Barfield, Richard, Basso, Daniela, Berndt, Sonja I., Boutron-Ruault, Marie-Christine, Brotzman, Michelle, Büchler, Markus W., Bueno-de-Mesquita, H. Bas, Bugert, Peter, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Capurso, Gabriele, Chung, Charles, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Funel, Niccola, Gaziano, J. Michael, Giese, Nathalia A., Giovannucci, Edward L., Goggins, Michael, Gorman, Megan J., Gross, Myron, Haiman, Christopher A., Hassan, Manal, Helzlsouer, Kathy J., Henderson, Brian E., Holly, Elizabeth A., Hu, Nan, Hunter, David J., Innocenti, Federico, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., LaCroix, Andrea, Landi, Maria T., Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Nakamura, Yusuke, Oberg, Ann L., Owzar, Kouros, Patel, Alpa V., Peeters, Petra H. M., Peters, Ulrike, Pezzilli, Raffaele, Piepoli, Ada, Porta, Miquel, Real, Francisco X., Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Taylor, Philip R., Theodoropoulos, George E., Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Wu, Chen, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Hartge, Patricia, Fuchs, Charles, Chanock, Stephen J., Stolzenberg-Solomon, Rachael S., Amundadottir, Laufey T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191666/
https://www.ncbi.nlm.nih.gov/pubmed/25086665
http://dx.doi.org/10.1038/ng.3052
Descripción
Sumario:We performed a multistage genome-wide association study (GWAS) 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 = 3.0×10(−12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2; OR = 1.46; 95% CI = 1.30–1.65; P = 1.1×10(−10)), rs9581943 at 13q12.2 (PDX1; OR = 1.15; 95% CI = 1.10–1.20; P = 2.4×10(−9)), and rs16986825 at 22q12.1 (ZNRF3; OR = 1.18; 95% CI = 1.12–1.25; P = 1.2×10(−8)). An independent signal was identified in exon 2 of TERT at the established region 5p15.33 (rs2736098; OR = 0.80; 95% CI = 0.76–0.85; P = 9.8×10(−14)). We also identified a locus at 8q24.21 (rs1561927; P = 1.3×10(−7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study has identified multiple new susceptibility alleles for pancreatic cancer worthy of follow-up studies.

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