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Role of NQO1 609C>T and NQO2 −3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis

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Abstract

Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case–control study was performed to investigated the associations of NQO1 609C>T and NQO2 −3423G>A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C>T and evaluated the association between the NQO1 609C>T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C>T and NQO2 −3423G>A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29–5.42 and OR = 1.88; 95 % CI = 1.02–3.49 respectively). Further, gene–gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C>T and NQO2 −3423G>A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C>T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98–14.19). Meta analysis of NQO 609C>T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C>T and NQO2 −3423G>A genetic variations modulate risk of EC in high-risk Kashmir population.

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Acknowledgments

The study was supported by a research grant from the Indian Council of Medical Research (ICMR), New Delhi. The authors thank Ms. Anshika Srivastava for her help in manuscript preparation.

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Authors and Affiliations

  1. Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareilly Road, Lucknow, 226014, India

    Manzoor Ahmad Malik & Balraj Mittal

  2. Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, 190011, India

    Showkat Ali Zargar

Authors
  1. Manzoor Ahmad Malik
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  2. Showkat Ali Zargar
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  3. Balraj Mittal
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Correspondence to Balraj Mittal.

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Malik, M.A., Zargar, S.A. & Mittal, B. Role of NQO1 609C>T and NQO2 −3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis. Mol Biol Rep 39, 9095–9104 (2012). https://doi.org/10.1007/s11033-012-1781-y

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  • DOI: https://doi.org/10.1007/s11033-012-1781-y

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