The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population

Abstract

Background: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. Aims: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. Subjects: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. Methods: We identified the IL-8 2251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. Results: IL-8 2251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 2251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in 2251A carriers than in T/T carriers. In the in vitro assay, IL-8 2251A showed enhanced promoter activity in response to IL-1b or tumour necrosis factor a. Conclusions: The IL-8 2251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

lnterleukin-8 gene polymorphism and susceptibility to gastric cancer in a brazilian population

“…The heterozygous A/T genotype increased more than twice the risk of GC (OR=2.50, 95% CI: 1.27-4.90; P=0.008). Similar results have been reported by Ohyauchi et al, (2005) who showed that this genotype was more frequent in patients with GC (OR=2.02, 95% CI: 1.37-2.97; P=0.0005). Sarvestani et al (2006) also compared the frequency of IL-8 (rs4073) genotypes between patients with gastritis, peptic ulcer and GC and found a higher prevalence of the A/A genotype in patients with GC compared to those with benign diseases (P=0.013).…”

“…This cytokine is involved in the infl ammatory response to infection with Helicobacter pylori, recruits phagocytes and causes damage to the gastric mucosa by inducing the release of reactive oxygen radicals (Torok et al, 2005;Ohyauchi et al, 2005). Furthermore, studies have shown that IL-8 induces cell proliferation and angiogenesis (Karashima et al, 2003;Taguchi et al, 2005).…”

“…These cytokines are important mediators in gastric physiology and pathophysiology and could play important roles in the etiology of GC (Sharma et al, 1998). There is growing interest in identifying the association between IL-8 (rs4073) genotypes and the risk of GC (Ohyauchi et al, 2005;Taguchi et al, 2005;Sarvestani et al, 2006;Shirai et al, 2006Persson et al, 2011.…”

Lack of Association of a Common Polymorphism in the 3'-UTR of Interleukin 8 with Non Small Cell Lung Cancer in Kashmir

“…Polymorphisms in pro-inflammatory factors could affect the body's inflammatory response by directly impacting the expression and function of certain inflammatory cytokines. Ohyauchi et al (2005) demonstrated that IL-8 -251 A is associated with higher IL-8 gene transcription and thus we evaluated this polymorphism in NSCLC patients of our population.…”

“…Elevated IL-8 levels were associated with disease progression and recurrence in human prostate, breast, lung and gastric cancers (Taguchi et al, 2005;Ahmed et al, 2006;Lurje et al, 2008;Millar et al, 2008). Recently, genetic polymorphisms of the IL-8 gene have been implicated in the susceptibility to a range of cancers, including Colon cancer (Ohyauchi et al, 2005), Gastric cancer (McCarron et al, 2002), Prostrate cancer (Ben et al, 2007) and nasopharyngeal cancer (David et al, 2008). In the backdrop of above cited studies, we hypothesize that the IL-8 promoter SNP which results in higher IL-8 secretion, was associated with increased risk of non small cell lung carcinoma.…”