Carcinogenesis Advance Access originally published online on February 2, 2007
Carcinogenesis 2007 28(6):1323-1328; 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
1 Department of Medical Genetics, Queen's University Belfast, Royal Group of Hospitals, Grosvenor Road, Belfast BT12 6BA
2 Centre for Clinical and Population Sciences, Queen's University Belfast, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ
3 Department of Medical Statistics, Queen's University Belfast, Mulhouse Building, Grosvenor Road, Belfast, BT12 6BJ
4 Department of Gastroenterology, Royal Group of Hospitals, Grosvenor Road, Belfast, BT12 6BA
5 National Cancer Registry Ireland, Elm Court, Boreenmonna Road, Cork, Ireland
6 Department of Thoracic Surgery, Royal Group of Hospitals, Grosvenor Road, Belfast, BT12 6BA
7 Department of Thoracic Surgery, St James's Hospital, James's Street, Dublin 8, Ireland
* To whom correspondence should be addressed at Division of Gastroenterology, Box 1069, Mount Sinai Medical Center, One Gustave Levy Place, New York, NY 10029-6574, USA. Tel: +1 212 659 9393; Fax: +1 212 659 9853; Email: s.murphy{at}qub.ac.uk
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. The Factors Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study is a population-based, case–control study of BE and EAC in Ireland. DNA from EAC (n = 207), BE (
3 cm BE at endoscopy with specialized intestinal metaplasia on biopsy, n = 189) and normal population controls (n = 223) were analyzed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPX2) were genotyped using multiplex polymerase chain reaction 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. Eleven SNPs were genotyped (six for GSTP1, three for MnSOD and two for GPX2); all were in Hardy–Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios for EAC for individual SNPs ranged from 0.68 [95% confidence interval (CI) 0.43–1.08] to 1.25 (95% CI 0.73–2.16), and for BE from 0.84 (95% CI 0.52–1.30) to 1.30 (95% CI 0.85–1.97). SNPs in all three genes were in strong linkage disequilibrium (D' > 0.887) but haplotype analysis did not show any significant association with EAC or BE. 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.
Abbreviations: BE, Barrett's esophagus; CI, confidence interval; EAC, esophageal adenocarcinoma; FINBAR, Factors Influencing the Barrett's Adenocarcinoma Relationship; GI, gastrointestinal; GPX2, glutathione peroxidase 2; GSTP1, glutathione S-transferase P1; MnSOD, manganese superoxide dismutase; OR, odds ratio; PCR, polymerase chain reaction; ROS, reactive oxygen species; SIM, specialized intestinal metaplasia; SNP, single-nucleotide polymorphism
Received November 6, 2006; revised December 13, 2006; accepted January 9, 2007.