Melchiades Jessica L, Zabaglia Luanna M, Sallas Mayara L, Orcini Wilson A, Chen Elizabeth, Smith Marilia A C, Payão Spencer L M, Rasmussen Lucas T
Universidade do Sagrado Coração (USC), Bauru, São Paulo, Brazil.
Departamento de Morfologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Cytokine. 2017 Aug;96:203-207. doi: 10.1016/j.cyto.2017.04.020. Epub 2017 Apr 27.
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♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). 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.
白细胞介素2（IL-2）是一种促炎细胞因子，主要由免疫调节性辅助性T细胞合成，在抗肿瘤免疫中发挥重要作用。幽门螺杆菌（H. pylori）是一种革兰氏阴性菌，可定植于胃黏膜并诱导IL-2的产生。这一过程会加剧炎症程度，并可能影响胃部疾病的发展。鉴于IL-2可能参与其中以及幽门螺杆菌在胃部疾病中的存在，本研究调查了IL-2基因多态性+114 T>G（rs2069763）和-330 T>G（rs2069762）与胃癌发生之间的可能关联；然后将这些关联与幽门螺杆菌的存在情况进行相关性分析。从294例消化不良患者（173例女性/123例男性）中获取胃活检样本。在这些样本中，181例为慢性胃炎样本（102例女性/79例男性），62例为完整胃黏膜样本（47例女性/15例男性），51例为胃癌样本（22例女性/29例男性）。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对+114 T>G和-330 T>G多态性进行特征分析。考虑到研究人群的遗传特征，并基于共显性模型，在胃组织正常的患者和胃癌患者中，发现携带IL-2 -330 GG基因型的受试者患胃癌的风险较高（比值比[OR]=6.43，95%置信区间[CI]：1.47 - 28.10，p=0.044）。数据针对幽门螺杆菌的存在情况进行了校正。在胃炎患者和胃癌患者中，发现携带IL-2 -330 GG基因型的受试者风险较高（OR=4.47，95% CI：1.84 - 10.84，p=0.0022）。当分析IL-2 +114多态性时，发现了类似结果。在胃组织正常的患者和胃癌患者中，发现携带+114 TT基因型的受试者患胃癌的风险较高（OR=5.97，95% CI：1.60 - 22.27，p=0.013）。该数据也针对幽门螺杆菌的存在情况进行了校正。在胃炎患者和胃癌患者中，发现携带+114 TT基因型的受试者风险较高（OR=6.36，95% CI：2.66 - 15.21，p<0.0001）。还对单倍型进行了分析。发现-330G/+114T单倍型与胃癌显著相关。因此，我们的结果表明，在幽门螺杆菌感染患者中，-330 GG和+114 TT基因型以及-330G/+114T单倍型均与患胃癌的高风险显著相关。
