Meta-analysis demonstrates lack of an association of microsomal epoxide hydrolase 1 polymorphisms with esophageal cancer risk

Abstract

ABSTRACT. Epoxide hydrolases metabolize exogenous chemicals, including carcinogens such as polycyclic aromatic hydrocarbons. The relationship between microsomal epoxide hydrolase 1 (EPHX1) polymorphisms and esophageal cancer risk has been investigated in various ethnic populations, but the results have been contradictory. We investigated the association of EPHX1 Tyr113His and His139Arg polymorphisms with esophageal cancer via a comprehensive metaanalysis. Publications before August 20, 2012 were included. Eight studies concerning Tyr113His polymorphism associated with 1158 esophageal cancer cases and 1868 controls were identified; 7 studies concerning association of His139Arg with 901 esophageal cancer cases and 1615 controls were also included. A random-effect model was applied, irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. No significant association was found in either the allele or genotype models for Tyr113His or His139Arg EPHX1 polymorphisms and esophageal cancer risk polymorphism with risk for esophageal cancer. Lack of association was also identified in stratified analyses by ethnicity. No publication bias was observed. We conclude that current evidence does not demonstrate association of EPHX1 Tyr113His or His139Arg polymorphisms with risk for development of esophageal cancer.

Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease

“…Low activity EPHX1 alleles harboring the rs1051740 SNP increased the risk of localized, but not advanced, prostate carcinoma (Catsburg et al 2012). However, recent meta-analyses have demonstrated the lack of association of rs1051740 or rs2234922 SNPs with the risk of breast, hepatocellular, and esophageal carcinomas (Hu et al 2013, Duan et al 2014). Lack of detailed investigation in sufficient sample sizes of gene-gene and gene-environment interactions presents the most probable reason for the reported inconsistencies.…”

Quantitative assessment of the influence of EPHX1 gene polymorphisms and cancer risk: a meta-analysis with 94,213 subjects

“…However, several studies [8][9][10] included in this meta-analysis were incorrectly classified according to source of controls, which may lead to an inaccurate result. Some recent studies did not evaluate the deviations from Hardy-Weinberg equilibrium (HWE) in control subjects [11][12][13], which could bias the estimates of genetic effects in genetic association studies and meta-analysis [14]. Since that date, several more studies have emerged to assess the relationship between the Tyr113His and/or His139Arg polymorphisms of the EPHX1 gene and susceptibility to a variety of cancers.…”