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

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 ≥3 studies were metaanalyzed 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 (ORBE = 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. © 2009 The Authors Journal compilation © 2009, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.