title: Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan.
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 polymorphism 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.
authors.affiliation: Division of Gastroenterology, Department of Therapeutic Medicine, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550 Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Taguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Shirai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mabuchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Itoh
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D016022:Case-Control Studies; D005260:Female; D005756:Gastritis / Q000209:etiology* / Q000235:genetics* / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013272:Stomach Diseases / Q000235:genetics / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000382:microbiology; D015854:Up-Regulation
chemical_list: D016209:Interleukin-8