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

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

Author information

1
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.

Abstract

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. .

PMID:
20484958
PMCID:
PMC2899150
DOI:
10.1159/000236023
[Indexed for MEDLINE]
Free PMC Article

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