Genome-wide association study identifies an early onset pancreatic cancer risk locus

Int J Cancer. 2020 Oct 15;147(8):2065-2074. doi: 10.1002/ijc.33004. Epub 2020 May 1.


Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10-4 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

Keywords: early onset; genome-wide association study; pancreatic cancer; single nucleotide polymorphisms; very early onset pancreatic cancer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Humans
  • Male
  • Middle Aged
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Supplementary concepts

  • Pancreatic Carcinoma