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10.1245/s10434-006-9290-7
Annals of Surgical Oncology 14:2250-2256 (2007)
© 2007 Society of Surgical Oncology
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Original Article

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

Su-Shun Lo3, Shu-Chun Lin1, Chew-Wun Wu3, Jen-Hao Chen3, Wen-I Yeh1, Ming-Yi Chung2 and Win-Yiu Lui3

1 School of Dentistry, National Yang Ming University, Taipei, Taiwan
2 Medical Education and Research Department, Taipei Veterans General Hospital, Taipei, Taiwan
3 Division of General Surgery, Taipei Veterans General Hospital and National Yang Ming University, No 201, Sec 2, Shih-Pai Rd, Taipei, Taiwan

Correspondence: Address correspondence and reprint requests to: Su-Shun Lo; E-mail: sslo{at}vghtpe.gov.tw

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.

Key Words: Gastric adenocarcinoma • Heme oxygenase • Heme oxygenase-1 promoter • Polymorphism

Abbreviations: CI, Confidence interval • HLA, Human leukocyte antigen • HO, Heme oxygenase • OR, Odds ratio






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