Carcinogenesis Advance Access published online on February 2, 2007
Carcinogenesis, doi:10.1093/carcin/bgm007
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A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma
Department of Medical Genetics and Centre for Clinical and Population Sciences, Queen's University Belfast
Seamus J Murphy, Centre for Clinical and Population Sciences and Medical Genetics, Queen's University Belfast
Anne E Hughes, Professor, Dept of Medical Genetics, Queen's University, Belfast
Chris C Patterson, Reader in Medical Statistics, Centre for Clinical and Population Sciences, Queen's University, Belfast
Lesley A Anderson, Centre for Clinical and Population Sciences, Queen's University, Belfast
Peter Watson, Consultant Gastroenterologist, Royal Group of Hospitals, Belfast
Brian T Johnston, Consultant Gastroenterologist, Royal Group of Hospitals, Belfast
Harry Comber, Director, National Cancer Registry, Cork, Ireland
Jim McGuigan, Consultant Thoracic Surgeon, Royal Group of Hospitals, Belfast
John V Reynolds, Professor of Surgery, St. James’ Hospital, Dublin
Liam J Murray, Professor, Cancer Epidemiology and Prevention Research Group, Centre for Clinical and Population Sciences, Queen's University Belfast
Correspondence to: Seamus J Murphy, Present-Levison Inflammatory Bowel Disease Fellow, Division of Gastroenterology, Box 1069, Mount Sinai Medical Center, One Gustave Levy Place, New York, NY 10029-6574. Telephone: (001) 212 659 9393, Fax: (001) 212 659 9853, Email: s.murphy{at}qub.ac.uk
Introduction: Oxidative stress appears to be important in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Single nucleotide polymorphisms (SNPs) of antioxidant enzyme genes may play a part in determining individual susceptibility to these diseases.
Methods: The FINBAR study is a population-based case-control study of BE and EAC in Ireland. DNA from EAC (n=207), BE (
3cm BE at endoscopy with specialised intestinal metaplasia on biopsy, n=189), and normal population controls (n=223) were analysed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD), and glutathione peroxidase 2 (GPX2) were genotyped using multiplex PCR and SNaPshotTM. The 
2 test was used to compare genotype and allele frequencies between case and control subjects. Linkage disequilibrium between SNPs was quantified using Lewontin's D' value and haplotype frequency estimates obtained using Haploview.
Results: Eleven SNPs were genotyped (6 for GSTP1, 3 for MnSOD, 2 for GPX2); all were in Hardy-Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios (OR) for EAC for individual SNPs ranged from 0.68 (95%CI 0.43-1.08) to1.25 (95%CI 0.73-2.16), and for BE from 0.84 (95% 0.52-1.30) to 1.30 (95%CI 0.85-1.97). SNPs in all 3 genes were in strong linkage disequilibrium (D’> 0.887) but haplotype analysis did not show any significant association with EAC or BE.
Conclusions: SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with BE or EAC. Further studies aimed at identifying susceptibility genes should focus on different antioxidant genes or different pathways.
Key Words: Barrett's esophagus • esophageal adenocarcinoma • association study • single nucleotide polymorphism • antioxidant enzymes • GSTP1 • MnSOD • GPX2
Received November 6, 2006; revised December 13, 2006; accepted January 9, 2007.