title: CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir.
abstract: The study analyzed the relationship between genetic polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 (CYP) 1A1 and CYP2E1 and esophageal squamous cell carcinoma (ESCC) in Kashmir, India. The different genotypes of CYP1A1 and CYP2E1 were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 526 ESCC cases and equal number of matched controls. Conditional logistic regression models were used to assess the association of various genotypes with ESCC, gene-gene, and gene-environment interactions. High risk of ESCC was found in participants who carried CYP1A1 Val/Val genotype (OR=2.87; 95 % CI=1.00-8.44) and the risk increased in such individuals when c1/c1 of CYP2E1 genotype was also present (OR=5.68; 95 % CI=1.09-29.52). Risk due to CYP1A1 Val/Val genotype was further enhanced (OR=8.55; 95 % CI=1.86-42.20) when the analysis was limited to ever smokers. Participants who carried CYP2E1 c1/c2 genotype showed an inverse relation (OR=0.27; 95 % CI=0.17-0.43) with ESCC. The inverse association of CYP2E1 c1/c2 genotype was retained when CYP1A1 Ile/Ile was also present (OR=0.18; 95 % CI=0.09-0.32), as well as when analysis was limited to ever smokers (OR=0.45; 95 % CI=0.23-0.90). Significant interaction was found between CYP1A1 (Val/Val) and CYP2E1 (c1/c1) genotypes (OR=1.30; 95 % CI=1.12-1.51; P=0.001) and between CYP1A1 (Val/Val) and smoking (OR=1.31; 95 % CI=1.01-1.69; P=0.043). The study suggests CYP1A1 Val/Val and CYP2E1 c1/c1 genotypes are significantly associated with ESCC risk.
authors: Department of Biochemistry, University of Kashmir, Srinagar, J&K, 190006, India.
authors: Gulzar Ahmad
authors: GA
authors: Bhat
authors: Idrees Ayoub
authors: IA
authors: Shah
authors: Muzamil Ashraf
authors: MA
authors: Makhdoomi
authors: Beenish
authors: B
authors: Iqbal
authors: Rumaisa
authors: R
authors: Rafiq
authors: Sumaiya
authors: S
authors: Nabi
authors: Akbar
authors: A
authors: Masood
authors: Mohd Maqbool
authors: MM
authors: Lone
authors: Nazir Ahmad
authors: NA
authors: Dar
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005838:Genotype; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D012306:Risk
chemical_list: D019392:Cytochrome P-450 CYP2E1; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1