Role of epoxide hydrolase 1 gene polymorphisms in esophageal cancer in a high-risk area in India.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Ihsan
Rakhshan
R
Institute of Pathology, New Delhi, India.
Chattopadhyay
Indranil
I
Phukan
Rupkumar
R
Mishra
Ashwani K
AK
Purkayastha
Joydeep
J
Sharma
Jagannath
J
Zomawia
Eric
E
Verma
Yogesh
Y
Mahanta
Jagadish
J
Saxena
Sunita
S
Kapur
Sujala
S
D000368:Aged; D000428:Alcohol Drinking / Q000208:ethnology; D001114:Areca / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004851:Epoxide Hydrolases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008409:Mastication; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology
D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human