Li Chun, Xia Harry Hua-Xiang, Xie Wei, Hu Zhengguo, Ye Mei, Li Jin, Cheng Hong, Zhang Xiaolian, Xia Bing
Department of Internal Medicine and Geriatrics, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, China.
J Gastroenterol Hepatol. 2007 Feb;22(2):234-9. doi: 10.1111/j.1440-1746.2006.04379.x.
Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients.
Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test.
The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases.
IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.
幽门螺杆菌是慢性胃炎和消化性溃疡疾病的主要病因,也是胃腺癌的明确致癌物。然而,其潜在的致病机制尚未完全明确。白细胞介素-1(IL-1)是幽门螺杆菌诱导胃炎症反应中的关键细胞因子。本研究旨在确定白细胞介素-1β(IL-1B)和白细胞介素-1受体拮抗剂(IL-1RN)基因的多态性及其与中国患者幽门螺杆菌感染和胃十二指肠疾病的关系。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对399例胃十二指肠疾病患者(129例慢性胃炎、127例十二指肠溃疡和143例非贲门胃癌)和264例健康对照者进行IL-1B -511和IL-1RN基因多态性基因分型。通过有效的血清学检测确定幽门螺杆菌感染状态。
非贲门胃癌幽门螺杆菌阳性患者中IL-1B -511 T等位基因频率显著高于非贲门胃癌幽门螺杆菌阴性患者(60%对46%,P = 0.0342,比值比[OR]=1.666,95%置信区间[CI]:1.045 - 2.656)和健康对照者(60%对48%,P = 0.0071,OR = 1.665,95%CI:1.149 - 2.412)。然而,该多态性与慢性胃炎和十二指肠溃疡无关。多因素逻辑回归分析确定,在幽门螺杆菌感染存在的情况下,IL-1B -511 T/T携带者状态是非贲门胃癌的独立危险因素(校正OR = 3.01,95%CI:1.27 - 7.11,P = 0.01),且IL-1B -511 T等位基因频率是患胃癌的增加危险因素(P = 0.03,校正OR = 2.29,95%CI:1.08 - 4.86)。IL-1RN基因多态性与幽门螺杆菌感染及其他胃十二指肠疾病之间无关联。
在中国人群的非贲门胃癌中,IL-1B -511 T等位基因与幽门螺杆菌感染相关。IL-1B -511基因多态性似乎在中国幽门螺杆菌感染患者的胃癌发生中起重要作用。