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

  • Author(s): 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 HM
  • 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
  • et al.

Published Web Location

https://doi.org/10.1038/ng.3052
Abstract

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.

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