title: EPHX1 polymorphisms do not modify esophageal carcinoma susceptibility             in Dutch Caucasians.
abstract: Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians.
authors.affiliation: Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands. p.dura@mdl.umcn.nl
authors.forename: Polat
authors.initials: P
authors.lastname: Dura
authors.forename: Caro V V
authors.initials: CV
authors.lastname: Bregitha
authors.forename: Rene H M
authors.initials: RH
authors.lastname: Te Morsche
authors.forename: Hennie M J
authors.initials: HM
authors.lastname: Roelofs
authors.forename: Jon O
authors.initials: JO
authors.lastname: Kristinsson
authors.forename: Theo
authors.initials: T
authors.lastname: Wobbes
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Witteman
authors.forename: Adriaan C I T L
authors.initials: AC
authors.lastname: Tan
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human