Microsomal epoxide hydrolase (EPHX1), slow (exon 3, 113His) and fast (exon 4, 139Arg) alleles confer susceptibility to squamous cell esophageal cancer.
Genetic polymorphisms in xenobiotic metabolizing enzymes may alter risk of various cancers. Present case-control study evaluated the influence of EPHX1 genetic variations on squamous cell esophageal cancer (ESCC) susceptibility in 107 patients and 320 controls. EPHX1 polymorphic alleles were genotyped by direct sequencing (exon 3, Tyr113His) or PCR-RFLP (exon 4, His139Arg). Patients with exon 3 genotypes (Tyr113His, His113His) and 113His allele were at risk of ESCC (OR(Tyr113His) 2.0, 95% CI=1.2-3.4, p=0.007; OR(His113His) 2.3 95% CI=1.0-5.2, p=0.03 and OR(His) 1.5, 95% CI=1.0-2.1, p=0.01). In contrast, individuals with exon 4, 139Arg allele were at low risk of cancer (OR 0.34, 95% CI=0.20-0.56, p=0.001). However, none of haplotype combinations of exon 3 (Tyr113His) and exon 4 (His139Arg) polymorphisms showed modulation of risk for ESCC. Sub-grouping of patients based on anatomical location of tumor predicted that patients with exon 3, His113His and Tyr113His genotypes were at higher risk for developing ESCC tumor at upper and middle third locations (OR 4.4, 95% CI=1.0-18.5, p=0.04; OR 2.5, 95% CI=1.3-5.0, p=0.005 respectively). The frequency of exon 4, His139Arg genotype was significantly lower in ESCC patients with lower third tumor location as compared to controls (14.8% vs. 36.3%, p=0.02). In case-only study, gene-environment interaction of EPHX1 genotypes with tobacco, alcohol and occupational exposures did not appear to modulate the cancer susceptibility. In conclusion, exon 3, Tyr113His genotype was associated with higher risk of ESCC particularly at upper and middle-third anatomical locations of tumor. However, His139Arg genotype of exon 4, exhibited low risk for ESCC as well as its clinical characteristics.
Jain
Meenu
M
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow-226014, India.
Tilak
Anup Raj
AR
Upadhyay
Rohit
R
Kumar
Ashwani
A
Mittal
Balraj
B
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004781:Environmental Exposure; D004851:Epoxide Hydrolases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D016273:Occupational Exposure; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012306:Risk; D012907:Smoking / Q000453:epidemiology
D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human