Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis

Dis Esophagus. 2009;22(7):571-87. doi: 10.1111/j.1442-2050.2009.00947.x. Epub 2009 Feb 13.

Abstract

Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in > or =3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val(105) conveys modest excess risk (odds ratio [OR](BE)= 1.50, 95% confidence interval [CI] 1.16-1.95; OR(EAC)= 1.20, 95% CI 0.94-1.54). No excess risk was observed with GSTM1 null (OR(BE)= 0.77, 95% CI: 0.56-1.08; OR(EAC)= 1.08, 95% CI: 0.79-1.48), GSTT1 null (OR(BE)= 1.35, 95% CI: 0.91-2.01; OR(EAC)= 0.84, 95% CI: 0.48-1.49), or CYP1A Val(462) (OR(EAC)= 0.89, 95% CI: 0.40-1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1(Ile105Val) as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / epidemiology*
  • Adenocarcinoma / genetics
  • Barrett Esophagus / enzymology
  • Barrett Esophagus / epidemiology*
  • Barrett Esophagus / genetics*
  • Case-Control Studies
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / genetics*
  • Genetic Predisposition to Disease / epidemiology*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Risk Factors