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Association of microsomal epoxide hydrolase exon 3 Tyr113His and exon 4 His139Arg polymorphisms with gastric cancer in India

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Abstract

Background

Microsomal epoxide hydrolase, an important phase II xenobiotic enzyme, exhibits polymorphisms at exon 3 (Tyr113His [T/C]) and exon 4 (His139Arg [A/G]), which modulate enzyme activity; this may affect susceptibility to cancers. We studied association between these polymorphisms and gastric cancer (GC).

Methods

In a prospective study, 77 patients with GC, 50 with peptic ulcer, and 160 healthy controls (HC) were genotyped for exon 3 (PCR-RFLP followed by sequencing) and exon 4 (PCR-RFLP). Helicobacter pylori was considered to be present if two of three tests (histology, rapid urease test, and IgG antibody) were positive.

Results

Tyr113His and His139Arg genotypes and haplotypes were comparable among groups. 113His carriers were commoner among H. pylori-negative patients with GC than HC (p-value = 0.019, odds ratio (OR) = 2.5, 95 % confidence interval (CI) = 1.2–5.4). Haplotype combination of exons 3 and 4 113Tyr-139Arg (TA) were associated with higher and reduced risk in patients with GC than HC in presence and absence of H. pylori (25 % vs. 11 %; p-value = 0.033, OR = 2.61, 95 % CI = 1.08–6.3 and 11.6 % vs. 28.7 %; p-value = 0.004, OR = 0.33, 95 % CI = 0.15–0.7, respectively).

Conclusions

Though 113Tyr-139Arg was associated with GC in presence of H. pylori, in its absence, it appeared to be protective. Exon 3, 113His, however, was associated with GC even in absence of H. pylori infection.

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Acknowledgments

The Indian Council of Medical Research, New Delhi, India provided financial support under project no. 5/13/24/2007-NCD-III. SK (F. No.10-2(5)/2007(ii)-E.U.II) and VJ were recipients of fellowships from the University Grants Commission, India.

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Authors and Affiliations

  1. Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India

    Ujjala Ghoshal & Virendra Jaiswal

  2. Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India

    Sushil Kumar, Shweta Tripathi & Uday C. Ghoshal

  3. Department of Genetic, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India

    Balraj Mittal

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  1. Ujjala Ghoshal
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  2. Sushil Kumar
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Correspondence to Ujjala Ghoshal.

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Ghoshal, U., Kumar, S., Jaiswal, V. et al. Association of microsomal epoxide hydrolase exon 3 Tyr113His and exon 4 His139Arg polymorphisms with gastric cancer in India. Indian J Gastroenterol 32, 246–252 (2013). https://doi.org/10.1007/s12664-013-0332-3

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