Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

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

Nat Commun 2018 02 8;9(1):556. Epub 2018 Feb 8.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

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). 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), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10). 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.

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http://dx.doi.org/10.1038/s41467-018-02942-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805680PMC
February 2018
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