A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma.
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 (> or =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 SNaPshottrade mark. The chi(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.
Murphy
Seamus J
SJ
Department of Medical Genetics, Queen's University Belfast, Royal Group of Hospitals, Grosvenor Road, Belfast, Ireland. s.murphy@qub.ac.uk
Hughes
Anne E
AE
Patterson
Chris C
CC
Anderson
Lesley A
LA
Watson
R G Peter
RG
Johnston
Brian T
BT
Comber
Harry
H
McGuigan
Jim
J
Reynolds
John V
JV
Murray
Liam J
LJ
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*
C117436:GPX2 protein, human; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi