Journal Article

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

Yu, Herbert, Pezzilli, Raffaele, Goodman, Gary E., Real, Francisco X., Hasan, Manal, Orlow, Irene, Hegyi, Peter, Klein, Eric A., Stolzenberg-Solomon, Rachael Z., Mannisto, Satu, Jacobs, Eric J., Silverman, Debra, Neoptolemos, John P., Khaw, Kay-Tee, Bamlet, William R., Sund, Malin, Mambrini, Andrea, Chen, Fei, Bracci, Paige M., M. Gaziano, J. Michael, Thornquist, Mark D., Tavano, Francesca, LeMarchand, Loic, Yu, Kai, Wentzensen, Nicolas, Obazee, Ofure, Patel, Alpa V., Kraft, Peter, Zhong, Jun, Porta, Miquel, Wang, Zhaoming, Borges, Michael, Cotterchio, Michelle, Kaaks, Rudolf, Fuchs, Charles, Berndt, Sonja I., Bueno-de-Mesquita, Bas, Giles, Graham G., Lee, I.-Min, Mohelníková-Duchoňová, Beatrice, Canzian, Federico, Landi, Stefano, Babic, Ana, Amundadottir, Laufey T., Brais, Lauren, Chung, Charles C., Mocci, Evelina, Hoover, Robert, Van Den Eeden, Stephen K., Gallinger, Steven, Peters, Ulrike, Li, Donghui, Lawlor, Rita T., Borgida, Ayelet, Holcatova, Ivana, Cavestro, Giulia Martina, Haiman, Christopher, Severi, Gianluca, Kooperberg, Charles, Goggins, Michael, Kulke, Matthew H., Visvanathan, Kala, Gazouli, Ma

2018

Overview

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. Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Macmillan Publishers,Nature Portfolio
• Subject: 38/91 / 45 / 45/43 / 631/67/1504/1713 / 631/67/2324 / Cancer / Carcinoma, Pancreatic Ductal - genetics / Chromosome 1 / Consortia / Càncer / Càncer de pàncrees / Databases, Genetic / Disease control / Gene mapping / Genetic Predisposition to Disease / Genome-Wide Association Study / Genomes / Hepatocyte Nuclear Factor 1-beta - genetics / Hepatocyte Nuclear Factor 4 - genetics / Humanities and Social Sciences / Humans / Intercellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins / Meta-analysis / multidisciplinary / Pancreas cancer / Pancreatic cancer / Pancreatic Neoplasms - genetics / Patients / Polymorphism, Single Nucleotide / Proteins - genetics / Quantitative trait loci / Repressor Proteins - genetics / Science / Science (multidisciplinary) / Tensins - genetics