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

Nat Commun. 2018 Feb 8;9(1):556. doi: 10.1038/s41467-018-02942-5.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • HNF1B protein, human
  • HNF4G protein, human
  • Hepatocyte Nuclear Factor 4
  • Intracellular Signaling Peptides and Proteins
  • NOC2L protein, human
  • Proteins
  • Repressor Proteins
  • TNS3 protein, human
  • Tensins
  • Ucma protein, human
  • Hepatocyte Nuclear Factor 1-beta