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CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir

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Tumor Biology

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.

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Acknowledgement

We are highly obliged to all the subjects who participated in this study. We are also thankful to all the consultants and all the paramedical staff at SKIMS for their valuable help during subject recruitment and sample collection. We are extremely grateful of Amir Almasi-Hashiani, Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran for his statistical assistance.

Conflict of interest

None.

Funding

The study was financially supported by research grant from Indian Council of Medical Research (ICMR), New Delhi under IRIS ID 5/13/37/2007/-NCD-111.

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Authors and Affiliations

  1. Department of Biochemistry, University of Kashmir, Srinagar, J&K, 190006, India

    Gulzar Ahmad Bhat, Idrees Ayoub Shah, Muzamil Ashraf Makhdoomi, Beenish Iqbal, Rumaisa Rafiq, Sumaiya Nabi, Akbar Masood & Nazir Ahmad Dar

  2. Department of Radiation Oncology, SK Institute of Medical Sciences, Srinagar, J&K, 190011, India

    Mohd Maqbool Lone

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  1. Gulzar Ahmad Bhat
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Correspondence to Nazir Ahmad Dar.

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Bhat, G.A., Shah, I.A., Makhdoomi, M.A. et al. CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir. Tumor Biol. 35, 5323–5330 (2014). https://doi.org/10.1007/s13277-014-1694-6

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