Pooling-based genome-wide association study implicates gamma-glutamyltransferase 1 (GGT1) gene in pancreatic carcinogenesis

Pancreatology. 2010;10(2-3):194-200. doi: 10.1159/000236023. Epub 2010 May 17.


Background/aims: Knowledge regarding genetic factors that influence pancreatic cancer risk is currently limited. To identify novel pancreatic cancer susceptibility loci, we conducted a two-stage genome-wide association study.

Methods: The Affymetrix Genome-Wide Human SNP Array 6.0 and DNA pooling were used in the screening stage. Twenty-six single-nucleotide polymorphisms (SNPs) were selected for follow-up. These 26 lead SNPs and additionally selected tagSNPs for the regions around the lead SNPs were evaluated by individual genotyping of the pooling population and an independent validation population.

Results: Of the lead SNPs, the strongest association was found with rs4820599 located in the gamma-glutamyltransferase 1 (GGT1) gene. This SNP was significantly associated with pancreatic cancer risk in the validation population and the combined dataset (p(allele-based) = 0.019 and p(allele-based) = 0.003, respectively). Statistically significant associations were also observed with two GGT1 tagSNPs: rs2017869 and rs8135987. Lead SNP rs4820599 is in high linkage disequilibrium (LD; pairwise r(2): 0.69) and tagSNP rs2017869 is in strong LD (pairwise r(2): 0.96) with SNP rs5751901, which has been reported to be associated with increased GGT1 serum levels. GGT is expressed in the pancreas and plays a key role in glutathione metabolism.

Conclusion: Our results suggest that common variation in the GGT1 gene may affect the risk of pancreatic cancer. .

Publication types

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

MeSH terms

  • Genome-Wide Association Study
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Polymorphism, Single Nucleotide
  • gamma-Glutamyltransferase / genetics*


  • gamma-Glutamyltransferase