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Role of Xenobiotic-Metabolizing Enzyme Gene Polymorphisms and Interactions with Environmental Factors in Susceptibility to Gastric Cancer in Kashmir Valley

  • ORIGINAL RESEARCH
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Abstract

Background

Kashmir Valley has elevated incidence rate of gastric cancer (GC) and several environmental, host genetic factors have been suspected for it. Xenobiotic carcinogen exposure and interindividual differences in its cellular metabolism may modulate susceptibility to GC.

Aim of the Study

The aim of this study is to investigate the role of genetic variants of xenobiotic-metabolizing genes with susceptibility to GC in Kashmir Valley.

Methods

A case–control study was performed in 303 subjects (108 GC and 195 healthy controls) to analyze the association of polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3, CYP1A1, and CYP2E1 genes in susceptibility to GC in Kashmir Valley. All subjects were genotyped through polymerase chain reaction–restriction fragment length polymorphism.

Results

GSTM1null and CYP2E1c1c2 genotypes imparted risk for GC (odds ratio [OR] = 1.98, 95% confidence interval [95%CI] = 1.22–3.21, P = 0.006 and OR = 2.56, 95%CI = 1.25–5.25, P = 0.010, respectively). GSTM3AB genotype/B allele was found to be associated with low risk for GC. Smokers and high salted tea consumers themselves were at higher risk for GC (OR = 8.98, 95%CI = 5.16–15.62, P = 0.0001 and OR = 14.78, 95%CI = 8.02–27.23, P = 0.0001, respectively). Cancer risk was further enhanced in smokers with the GSTM1null genotype.

Conclusion

The results suggest that GSTM1null, GSTM3AB, and CYP2E1c1c2 genotypes modulate the risk of GC whereas GSTM1null genotypes enhance the risk of GC for smokers in the Kashmir population.

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Acknowledgment

The study was supported by a research grant from Indian Council of Medical Research, New Delhi. The authors thank Mr. Bashir Ahmad, Ghulam Mustafa, and the faculty members of the Gastroenterology Department, SKIMS, Srinagar for their help in the sample collection.

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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 A. Malik, Rohit Upadhyay, Rama D. Mittal & Balraj Mittal

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

    Showket A. Zargar

  3. Department of Biotechnology, Babasaheb Bhimrao Amabedkar University, Lucknow, 226025, India

    Dinesh R. Modi

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  1. Manzoor A. Malik
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Correspondence to Balraj Mittal.

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Malik, M.A., Upadhyay, R., Mittal, R.D. et al. Role of Xenobiotic-Metabolizing Enzyme Gene Polymorphisms and Interactions with Environmental Factors in Susceptibility to Gastric Cancer in Kashmir Valley. J Gastrointest Canc 40, 26–32 (2009). https://doi.org/10.1007/s12029-009-9072-0

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