Heme Oxygenase-1 gene promoter polymorphism is associated with risk of gastric adenocarcinoma and lymphovascular tumor invasion

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.