Portal de Periódicos da CAPES

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

2014; Nature Portfolio; Volume: 46; Issue: 9 Linguagem: Inglês

10.1038/ng.3052

1546-1718

Brian M. Wolpin, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M. Petersen, Zhaoming Wang, Alan A. Arslan, Laura E. Beane Freeman, Paige M. Bracci, Julie E. Buring, Federico Canzian, Eric J. Duell, Steven Gallinger, Graham G. Giles, Gary E. Goodman, Phyllis J. Goodman, Eric J. Jacobs, Aruna Kamineni, Alison P. Klein, Laurence N. Kolonel, Matthew H. Kulke, Donghui Li, Núria Malats, Sara H. Olson, Harvey A. Risch, Howard D. Sesso, Kala Visvanathan, Emily White, Wei Zheng, Christian C. Abnet, Demetrius Albanes, Gabriella Andreotti, Melissa A. Austin, Richard Barfield, Daniela Basso, Sonja I. Berndt, Marie‐Christine Boutron‐Ruault, Michelle Brotzman, Markus W. Büchler, H. Bas Bueno‐de‐Mesquita, Peter Bugert, Laurie Burdette, Daniele Campa, Neil E. Caporaso, Gabriele Capurso, Charles C. Chung, Michelle Cotterchio, Eithne Costello, Joanne W. Elena, Niccola Funel, J. Michael Gaziano, Nathalia A. Giese, Edward L. Giovannucci, Michael Goggins, Megan J. Gorman, Myron D. Gross, Christopher A. Haiman, Manal M. Hassan, Kathy J. Helzlsouer, Brian E. Henderson, Elizabeth A. Holly, Nan Hu, David J. Hunter, Federico Innocenti, Mazda Jenab, Rudolf Kaaks, Timothy J. Key, Kay‐Tee Khaw, Eric A. Klein, Manolis Kogevinas, Vittorio Krogh, Juozas Kupčinskas, Robert C. Kurtz, Andrea Z. LaCroix, Maria Teresa Landi, Stefano Landi, Loı̈c Le Marchand, Andrea Mambrini, Satu Männistö, Roger L. Milne, Yusuke Nakamura, Ann L. Oberg, Kouros Owzar, Alpa V. Patel, Petra H. Peeters, Ulrike Peters, Raffaele Pezzilli, Ada Piepoli, Miquel Porta, Francisco X. Real, Elio Ríboli, Nathaniel Rothman, Aldo Scarpa, Xiao‐Ou Shu, Debra T. Silverman, Pavel Souček, Malin Sund, Renata Talar‐Wojnarowska, Philip R. Taylor, George Theodoropoulos, Mark Thornquist, Anne Tjønneland, Geoffrey S. Tobias, Dimitrios Trichopoulos, Pavel Vodička, Jean Wactawski‐Wende, Nicolas Wentzensen, Chen Wu, Herbert Yu, Kai Yu, Anne Zeleniuch‐Jacquotte, Robert N. Hoover, Patricia Hartge, Charles S. Fuchs, Stephen J. Chanock, Rachael S. Stolzenberg-Solomon, Laufey T. Ámundadóttir,

Epigenetics and DNA Methylation

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 × 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)). 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 × 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 identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.