Role of epoxide hydrolase 1 gene polymorphisms in esophageal cancer in a high‐risk area in India

Abstract

Microsomal epoxide hydrolase 1 (EPHX1) is involved in the metabolism of environmental and tobacco carcinogens. Tobacco smoking, betel quid chewing, and alcohol consumption are the major known risk factors for esophageal cancer. The present case-control study evaluated the influence of EPHX1 genetic variations on esophageal cancer susceptibility in 142 patients and 185 healthy controls from a high-incidence region of India where tobacco use and alcohol consumption are widespread and the users of these two substances are also betel quid chewers. EPHX1 polymorphic alleles (exon 3, Tyr113His and exon 4, His139Arg) were genotyped by polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing. The results were analyzed using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). Patients with exon 4 genotypes (139His/Arg, 139Arg/Arg) and the 139Arg allele were significantly associated with a risk of esophageal cancer (OR(His139Arg) 1.887, 95% CI = 1.112-3.201, P = 0.019; OR(Arg139Arg) 7.140, 95% CI = 1.276-393.953, P = 0.025 and OR(Arg) 1.83, 95% CI = 1.19-2.82, P = 0.003). The 139His/Arg genotype was a significant risk factor for esophageal cancer in tobacco chewers and betel quid chewers. Patients with the 139Arg/Arg genotype were at significantly higher risk for developing a well-differentiated and moderately-differentiated grade of tumor. In contrast, the 113His/His genotype of exon 3 was a significant protective factor for esophageal cancer in tobacco smokers (OR 0.291, 95% CI = 0.138-0.616, P = 0.001), betel quid chewers (OR 0.434, 95% CI = 0.236-0.797, P = 0.007), and alcohol users. EPHX1 exon 4 139His/Arg, and 139Arg/Arg genotypes were associated with a higher risk of esophageal cancer in a high-risk area of India.