Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori

Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori

Author Melchiades, Jessica L. Google Scholar
Zabaglia, Luanna M. Google Scholar
Sallas, Mayara L. Google Scholar
Orcini, Wilson A. Google Scholar
Chen, Elizabeth Autor UNIFESP Google Scholar
Smith, Marilia A. C. Autor UNIFESP Google Scholar
Payao, Spencer L. M. Google Scholar
Rasmussen, Lucas T. Google Scholar
Abstract Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms + 114 T > G (rs2069763) and -330 T > G (rs2069762) and the development of gastric cancer

these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173 female/123 male). Of these samples, 181 were chronic gastritis samples (102 female/79), 62 were samples of intact gastric mucosa (47 female/15 male), and 51 were samples of gastric cancer (22 female/29 male). PCR-RFLP was used to characterize the +114 T > G and 330 T > G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR = 6.43, 95% CI: 1.47-28.10, p = 0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR = 4.47, 95% CI: 1.84-10.84, p = 0.0022). When the IL-2 + 114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR = 5.97, 95% CI: 1.60-22.27, p = 0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR = 6.36, 95% CI: 2.66-15.21, p < 0.0001). The haplotype was also analyzed. The 330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the 330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the 330G/+114T haplotype.
Keywords Helicobacter pylori
IL-2
-330 Polymorphism
+114 Polymorphism
Gastric cancer
Language English
Sponsor Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) [2014/239430, 2015/11371-7, 2015/116139]
Grant number FAPESP: 2014/239430
FAPESP: 2015/11371-7
FAPESP: 2015/116139
Date 2017
Published in Cytokine. London, v. 96, p. 203-207, 2017.
ISSN 1043-4666 (Sherpa/Romeo, impact factor)
Publisher Academic Press Ltd- Elsevier Science Ltd
Extent 203-207
Origin http://dx.doi.org/10.1016/j.cyto.2017.04.020
Access rights Closed access
Type Article
Web of Science ID WOS:000405042800028
URI http://repositorio.unifesp.br/handle/11600/51497

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