Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan

Ayumu Taguchi, Naoki Ohmiya, Kennosuke Shirai, Nobuyuki Mabuchi, Akihiro Itoh, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Host genetic susceptibility may influence gastric carcinogenesis caused by Helicobacter pylori infection. We aimed to clarify the relationship of interleukin (IL)-8 polymorphism with the risk of atrophic gastritis and gastric cancer. We examined IL-8 -251 T > A, IL-1B -511 C > T, and IL-1RN intron 2 polymorphisms in 252 healthy controls, 215 individuals with atrophic gastritis, and 396 patients with gastric cancer. We also investigated the effect of the IL-8 polymorrphism on IL-8 production and histologic degree of gastritis in noncancerous gastric mucosa. Although no correlation was found in the analysis of the IL-1B and IL-1RN polymorphisms, IL-8 -251 A/A genotype held a higher risk of atrophic gastritis [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.12-4.94] and gastric cancer (OR, 2.22; 95% CI, 1.08-4.56) compared with the T/T genotype. We also found that the A/A genotype increased the risk of upper-third location (OR, 3.66; 95% CI, 1.46-9.17), diffuse (OR, 2.79; 95% CI, 1.21-6.39), poorly differentiated (OR, 2.70; 95% CI, 1.14-6.38), lymph node (OR, 2.50; 95% CI, 1.01-6.20), and liver metastasis (OR, 5.63; 95% CI, 1.06-30.04), and p53 -mutated (OR, 1.91; 95% CI, 1.13-3.26) subtypes of gastric cancer. The A/A and A/T genotypes were significantly associated with higher levels of IL-8 protein compared with the T/T genotype. Neutrophil infiltration score was significantly higher in the A/A genotype than in the T/T genotype. In conclusion, we showed that the IL-8 -251 T > A polymorphism is associated with higher expression of IL-8 protein, more severe neutrophil infiltration, and increased risk of atrophic gastritis and gastric cancer.

Original languageEnglish
Pages (from-to)2487-2493
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number11 I
DOIs
Publication statusPublished - 01-11-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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