Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Klein, Alison P 
Wolpin, Brian M 
Risch, Harvey A 
Stolzenberg-Solomon, Rachael Z 

Abstract

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.

Description

Keywords

Carcinoma, Pancreatic Ductal, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Humans, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, Proteins, Repressor Proteins, Tensins

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (G1000143)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Medical Research Council (G0401527)
Cancer Research Uk (None)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
National Institute for Health Research (NIHR) (NF-SI-0512-10114)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)