Pooling-based Genome-wide Association Study Implicates Gamma-glutamyltransferase 1 (GGT1) Gene in Pancreatic Carcinogenesis

Overview

Journal Pancreatology

Specialties Endocrinology
Gastroenterology

Date 2010 May 21

PMID 20484958

Citations 28

Authors

Brenda Diergaarde

Randall Brand

Janette Lamb

Soo Yeon Cheong

Kim Stello

M Michael Barmada

Eleanor Feingold

David C Whitcomb

Affiliations

Soon will be listed here.

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. .

Citing Articles

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Genetic polymorphisms of GGT1 gene (rs8135987, rs5751901 and rs2017869) are associated with neoadjuvant chemotherapy efficacy and toxicities in breast cancer patients.

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