title: Polymorphisms in the microsomal epoxide hydrolase gene: role in lung cancer susceptibility and prognosis.
abstract: OBJECTIVE
  The aim of this study was to investigate the relationship between EPHXI exon 3 Tyr113His and exon 4 His139Arg polymorphisms, predicted microsomal epoxide hydrolase (mEH) activity, and lung cancer development. mEH is a protective enzyme involved in oxidative defences against a number of environmental chemicals and pollutants, but it is also responsible for the xenobiotic activation of carcinogens.
  
  
  METHODS
  We investigated the two polymorphisms of the mEH gene (EPHX1) in 58 lung cancer patients and 41 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  The exon 3 Tyr113His polymorphism was associated with lung cancer (P < 0.001). The frequency of the His113His homozygote genotype in exon 3 was significantly increased in patients compared with controls (P < 0.001). In contrast, there was no significant difference in exon 4 polymorphisms between patients and controls. When the exon 3 and 4 polymorphisms were considered together, the combined EPHX1 His113His113/His139His139 genotype (very low predicted enzyme activity) was found to be associated with an increased risk of lung cancer (P = 0.044, OR = 3.063, CI = 0.932-10.069). We observed that patients with T3 + T4 tumors had an approximately 3-fold higher risk of the Tyr113/His113 genotype than patients with T1 + T2 tumors. Lung cancer patients carrying a heterozygote Tyr113/His 113 genotype had a 2-fold increased risk of lymph node metastases (P = 0.051).
  
  
  CONCLUSIONS
  These findings suggest that the exon 3 Tyr113His and exon 4 His139Arg polymorphisms of EPHXI may be associated with a increased risk of lung cancer and a worse prognosis.
authors.affiliation: Department of Medicine, Institute of Experimental Medical Research, University of Istanbul, Istanbul, Turkey.
authors.forename: Zelal
authors.initials: Z
authors.lastname: Erkisi
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim-Eraltan
authors.forename: Akif
authors.initials: A
authors.lastname: Turna
authors.forename: Uzay
authors.initials: U
authors.lastname: Görmüs
authors.forename: Hakan
authors.initials: H
authors.lastname: Camlica
authors.forename: Turgay
authors.initials: T
authors.lastname: Isbir
mesh_terms: D000368:Aged; D001120:Arginine; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006639:Histidine; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects; D014443:Tyrosine
chemical_list: D014443:Tyrosine; D006639:Histidine; D001120:Arginine; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human