Seno Hiroshi, Satoh Kiichi, Tsuji Shingo, Shiratsuchi Takayuki, Harada Yosuke, Hamajima Nobuyuki, Sugano Kentaro, Kawano Sunao, Chiba Tsutomu
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Gastroenterol Hepatol. 2007 May;22(5):729-37. doi: 10.1111/j.1440-1746.2007.04934.x.
Helicobacter pylori (H. pylori)-induced chronic atrophic gastritis is a high-risk factor for gastric cancer. Immune responses to H. pylori are involved in gastric mucosal inflammation, and might affect clinical outcome, including the development of gastric cancer. The present study examines the significance of gene polymorphisms of various cytokines in the development of gastric cancer following H. pylori infection.
One hundred Japanese non-cardia gastric cancer patients and 93 dyspeptic patients as controls were enrolled in the study (age range 50-75 years). All patients were positive for H. pylori. Genomic DNA was extracted from peripheral whole blood leukocytes, and we comprehensively analyzed 207 single nucleotide polymorphisms (SNP) in 11 cytokine genes; interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist (RN), IL-4, IL-4R, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, and IFN-gamma, using either invader assay (163 SNP), direct sequencing (22 SNP), or PCR-restriction fragment length polymorphism (22 SNP).
Among the 207 SNP examined, the IL-4 gene diplotypes (984 and 2983 AA/GA) had a significant negative association with gastric cancer development (odds ratio =0.3, 95% confidence interval =0.1-0.9). When we adopted the dyspeptic patients over 66 years of age as the controls, the IL-1RN gene diplotypes (-1102 and 6110 CG/GA) also had a significant negative association (odds ratio =0.2, 95% confidence interval =0.1-0.7).
A comprehensive analysis of 207 SNP of 11 cytokine genes revealed that variations in IL-4 and IL-1RN genes are negatively associated with the risk of developing gastric cancer following H. pylori infection. Distinct host cytokine responses in the gastric mucosa might have a role in H. pylori-induced carcinogenesis.
幽门螺杆菌（H. pylori）诱发的慢性萎缩性胃炎是胃癌的高危因素。对幽门螺杆菌的免疫反应参与胃黏膜炎症，且可能影响临床结局，包括胃癌的发生。本研究探讨各种细胞因子基因多态性在幽门螺杆菌感染后胃癌发生中的意义。
本研究纳入100例日本非贲门胃癌患者和93例消化不良患者作为对照（年龄范围50 - 75岁）。所有患者幽门螺杆菌检测均为阳性。从外周全血白细胞中提取基因组DNA，我们使用侵入法（163个单核苷酸多态性）、直接测序法（22个单核苷酸多态性）或聚合酶链反应 - 限制性片段长度多态性（22个单核苷酸多态性），对11种细胞因子基因中的207个单核苷酸多态性（SNP）进行全面分析；这些细胞因子基因包括白细胞介素（IL）-1α、IL - 1β、IL - 1受体拮抗剂（RN）、IL - 4、IL - 4R、IL - 8、IL - 10、IL - 12、肿瘤坏死因子（TNF）-α、TNF - β和干扰素 - γ。
在检测的207个单核苷酸多态性中，IL - 4基因双倍型（984和2983 AA/GA）与胃癌发生呈显著负相关（比值比 = 0.3，95%置信区间 = 0.1 - 0.9）。当我们将66岁以上的消化不良患者作为对照时，IL - 1RN基因双倍型（-1102和6110 CG/GA）也呈显著负相关（比值比 = 0.2，95%置信区间 = 0.1 - 0.7）。
对11种细胞因子基因的207个单核苷酸多态性进行全面分析显示，IL - 4和IL - 1RN基因的变异与幽门螺杆菌感染后发生胃癌的风险呈负相关。胃黏膜中不同的宿主细胞因子反应可能在幽门螺杆菌诱导的致癌过程中起作用。
