Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
Authors: 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 , Zhong Jun , Chen Fei , Albanes Demetrius , Andreotti Gabriella , Arslan Alan A. , Babic Ana , Bamlet William R. , Beane-Freeman Laura , Berndt Sonja I. , Blackford Amanda , Borges Michael , Borgida Ayelet , Bracci Paige M. , Brais Lauren , Brennan Paul , Brenner Hermann , Bueno-de-Mesquita Bas , Buring Julie , Campa Daniele , Capurso Gabriele , Cavestro Giulia Martina , Chaffee Kari G. , Chung Charles C. , Cleary Sean , Cotterchio Michelle , Dijk Frederike , Duell Eric J. , Foretova Lenka , Fuchs Charles , Funel Niccola , Gallinger Steven , M. Gaziano J. Michael , Gazouli Maria , Giles Graham G. , Giovannucci Edward , Goggins Michael , Goodman Gary E. , Goodman Phyllis J. , Hackert Thilo , Haiman Christopher , Hartge Patricia , Hasan Manal , Hegyi Peter , Helzlsouer Kathy J. , Herman Joseph , Holcatova Ivana , Holly Elizabeth A. , Hoover Robert , Hung Rayjean J. , Jacobs Eric J. , Jamroziak Krzysztof , Janout Vladimir , Kaaks Rudolf , Khaw Kay-Tee , Klein Eric A. , Kogevinas Manolis , Kooperberg Charles , Kulke Matthew H. , Kupcinskas Juozas , Kurtz Robert J. , Laheru Daniel , Landi Stefano , Lawlor Rita T. , Lee I.-Min , LeMarchand Loic , Lu Lingeng , Malats Núria , Mambrini Andrea , Mannisto Satu , Milne Roger L. , Mohelníková-Duchoňová Beatrice , Neale Rachel E. , Neoptolemos John P. , Oberg Ann L. , Olson Sara H. , Orlow Irene , Pasquali Claudio , Patel Alpa V. , Peters Ulrike , Pezzilli Raffaele , Porta Miquel , Real Francisco X. , Rothman Nathaniel , Scelo Ghislaine , Sesso Howard D. , Severi Gianluca , Shu Xiao-Ou , Silverman Debra , Smith Jill P. , Soucek Pavel , Sund Malin , Talar-Wojnarowska Renata , Tavano Francesca , Thornquist Mark D. , Tobias Geoffrey S. , Van Den Eeden Stephen K. , Vashist Yogesh , Visvanathan Kala , Vodicka Pavel , Wactawski-Wende Jean , Wang Zhaoming , Wentzensen Nicolas , White Emily , Yu Herbert , Yu Kai , Zeleniuch-Jacquotte Anne , Zheng Wei , Kraft Peter , Li Donghui , Chanock Stephen , Obazee Ofure , Petersen Gloria M. , Amundadottir Laufey T. 
Published: February 2018

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.