Genetic polymorphisms in the mEH gene in relation to tobacco smoking: role in lung cancer susceptibility and survival in north Indian patients with lung cancer undergoing platinum-based chemotherapy

Lay abstract Microsomal epoxide hydrolase (mEH) is an enzyme that plays a defensive role against chemicals. In this study, the relationship between the variation of the epoxide hydrolase and the risk of lung cancer was investigated and its role in the survival of patients with lung cancer was evaluated. The study comprised 550 cases and 550 controls. Genotyping was carried out using molecular biology tools and was followed by statistical analysis. The variant genotype of the EPHX1 gene was not associated with the risk of lung cancer, even based on histology. The variant form of the EPHX1 gene was found to be a risk factor for smokers. The Tyr/His genotype was associated with the risk of lung cancer in male subjects. Patients carrying the variant form of the EPHX1 gene (His(139)Arg) experienced better survival. The heterozygous genotype of the EPHX1Tyr(113)His gene was related to longer survival time in patients who received cisplatin/carboplatin along with irinotecan. The EPHX1 Tyr(113)His polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS of patients with small-cell lung cancer (SCLC) after irinotecan therapy and might increase the likelihood of lymph node metastasis; EPHX1His(139)Arg exhibited better survival, especially in patients with SCLC. Aim: Epoxide hydrolase is involved in oxidative defenses and is responsible for the activation of carcinogens. The relationship between EPHX1 polymorphisms (Tyr(113)His and His(139)Arg) and overall survival (OS) and lung cancer (LC) risk was investigated. Methods: The study comprised 550 cases and 550 controls. Genotyping and statistical analysis were applied. Results: The variant genotypes of EPHX1 polymorphisms exhibited no association with LC risk. The Tyr(113)His polymorphism exhibited twofold increased odds of lymph node invasion (p = 0.04). The Tyr/His genotype is a risk factor for smokers. Subjects carrying the combined genotype for His(139)Arg showed better median survival time (MST) and the heterozygous genotype revealed better MST in the case of small-cell lung cancer (SCLC; 11.30 vs 6.73 months; log-rank test: p = 0.02). The heterozygous genotype (His139Arg) had longer MST in patients receiving cisplatin/carboplatin and irinotecan (11.30 vs 7.23; log-rank test: p = 0.007) Conclusion: The Tyr(113)His polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS in patients with SCLC after irinotecan.