Polymorphisms in the microsomal epoxide hydrolase gene: role in lung cancer susceptibility and prognosis.

Abstract

AIMS AND BACKGROUND:

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).

CONCLUSION:

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: Zelal Erkisi, Ilhan Yaylim-Eraltan, Akif Turna, Uzay Görmüs, Hakan Camlica, Turgay Isbir
• Journal: Tumori (Tumori) 2010 Sep-Oct Vol. 96 Issue 5 Pg. 756-63 ISSN: 0300-8916 [Print] United States
• PMID: 21302624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tyrosine
• Histidine
• Arginine
• Epoxide Hydrolases
• EPHX1 protein, human

Topics

• Aged
• Arginine
• Carcinoma (enzymology, genetics)
• Carcinoma, Squamous Cell (genetics)
• Case-Control Studies
• Epoxide Hydrolases (genetics)
• Exons
• Female
• Genetic Predisposition to Disease
• Histidine
• Humans
• Lung Neoplasms (enzymology, etiology, genetics)
• Male
• Microsomes (enzymology)
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Predictive Value of Tests
• Prognosis
• Smoking (adverse effects)
• Tyrosine