Ota Masafumi, Tahara Tomomitsu, Otsuka Toshimi, Jing Wu, Nomura Tomoe, Hayashi Ranji, Shimasaki Takeo, Nakamura Masakatsu, Shibata Tomoyuki, Arisawa Tomiyasu
Department of Gastroenterology, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan.
Department of Gastroenterology, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Oncol Lett. 2018 Mar;15(3):3772-3778. doi: 10.3892/ol.2018.7785. Epub 2018 Jan 12.
The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (), which encodes a component of the nucleotide binding oligomerization domain containing 2-RIP2 pathway, may compromise the innate immune response to infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro-duodenal endoscopy. Overall, the rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer [OR, 1.37; 95% confidence interval (CI), 1.06-1.77; P=0.016], particularly of the intestinal type (OR, 1.53; 95% CI, 1.13-2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI, 1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild-type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type.
本研究旨在调查编码含核苷酸结合寡聚化结构域2-RIP2途径一个组分的受体相互作用丝氨酸/苏氨酸激酶2（RIP2）中的单核苷酸多态性是否会损害对幽门螺杆菌感染的天然免疫反应，从而导致日本人群患胃癌的易感性增加。本病例对照研究调查了528例胃癌患者和697例经上消化道十二指肠内镜检查无胃部恶性肿瘤的患者中RIP2单核苷酸多态性与胃黏膜炎症、萎缩及癌症易感性之间的关联。总体而言，RIP2基因rs16900627的次要等位基因与胃癌易感性显著相关[比值比（OR）为1.37；95%置信区间（CI）为1.06 - 1.77；P = 0.016]，尤其是肠型胃癌（OR为1.53；95% CI为1.13 - 2.07；P = 0.0062）。它还与胃黏膜萎缩显著相关（OR为1.83；95% CI为1.14 - 2.93；P = 0.011）。使用更新的悉尼系统评估慢性胃炎的严重程度时，rs16900627次要等位基因携带者的活动度和炎症评分以及萎缩和化生评分均显著高于野生型纯合子。在年龄小于60岁的患者中，rs16900627次要等位基因携带者的胃蛋白酶原I/II比值显著低于野生型纯合子（P = 0.037）。rs16900627次要等位基因与胃黏膜炎症的严重程度及胃黏膜萎缩的发生相关。该等位基因的携带者患胃癌尤其是肠型胃癌的风险可能增加。
