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Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion

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Abstract

Purpose

Heme oxygenase-1 (HO-1) gene, which encodes an oxidative response protein, plays a role in cytoprotection. A (GT) n dinucleotide repeat in HO-1 promoter is polymorphic and modulates the transcriptional activity of the gene. A HO-1 gene promoter polymorphism was reported to be associated with the risks of lung adenocarcinoma and oral squamous cancer. In this study, the correlation between the HO-1 gene promoter polymorphism and the clinicopathological characteristics, along with the risk of gastric cancer, was analyzed.

Experimental design

We examined the genotypic frequencies of (GT) n repeats in 183 gastric cancer patients and 250 control subjects by PCR-based genotyping and DNA sequencing. The length polymorphisms of (GT) n repeats were classified into short (S) component (n ≤ 25), medium (M) component (26 ≤ n ≤ 30) and long (L) component (n ≥ 31). The distribution of S, M and L components in patient and control groups were evaluated to determine the correlation with susceptibility and clinicopathological characteristics of gastric adenocarcinoma.

Results

Higher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L genotype were found in gastric cancer patients. The frequencies of M-allele, M-allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in patients with gastric cancer than controls. Furthermore, the frequency of lymphovascular tumor invasion was significantly lower in M-allele carriers compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009).

Conclusions

These findings suggest that the long (GT) n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT) n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.

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FIG. 1.

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Abbreviations

CI:

confidence interval;

HLA:

human leukocyte antigen;

HO:

heme oxygenase;

OR:

odds ratio;

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Authors and Affiliations

  1. School of Dentistry, National Yang Ming University, Taipei, Taiwan

    Shu-Chun Lin & Wen-I Yeh

  2. Medical Education and Research Department, Taipei Veterans General Hospital, Taipei, Taiwan

    Ming-Yi Chung

  3. Division of General Surgery, Taipei Veterans General Hospital and National Yang Ming University, No 201, Sec 2, Shih-Pai Rd, Taipei, Taiwan

    Su-Shun Lo, Chew-Wun Wu, Jen-Hao Chen & Win-Yiu Lui

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  1. Su-Shun Lo
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Correspondence to Su-Shun Lo.

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Grant sponsor:

This grant was supported by a grant from the Taipei Veterans General Hospital (VGH94-249) and partly from the National Science Council (NSC93-2314-B104), Taiwan.

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Lo, SS., Lin, SC., Wu, CW. et al. Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion. Ann Surg Oncol 14, 2250–2256 (2007). https://doi.org/10.1245/s10434-006-9290-7

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  • DOI: https://doi.org/10.1245/s10434-006-9290-7

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