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Published on: May 10, 2024
Polymorphisms in the microsomal epoxide hydrolase gene: role in lung cancer susceptibility and prognosis
Zelal Erkisi1, Ilhan Yaylim-Eraltan, Akif Turna
1Department of Medicine, Institute of Experimental Medical Research, University of Istanbul, Istanbul, Turkey.
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.
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