幽门螺杆菌相关远端胃癌与欧洲南部人群中HLA II类基因DQB10602及cagA菌株的关联

Association of Helicobacter pylori-related distal gastric cancer with the HLA class II gene DQB10602 and cagA strains in a southern European population.

作者信息

Quintero Enrique, Pizarro M Angeles, Rodrigo Luis, Piqué Josep M, Lanas Angel, Ponce Julio, Miño Gonzalo, Gisbert Javier, Jurado Aurora, Herrero M José, Jiménez Alejandro, Torrado Julio, Ponte Ana, Díaz-de-Rojas Francisco, Salido Eduardo

机构信息

Gastroenterology Department, University Hospital of the Canary Islands, Spain.

出版信息

Helicobacter. 2005 Feb;10(1):12-21. doi: 10.1111/j.1523-5378.2005.00287.x.

DOI:10.1111/j.1523-5378.2005.00287.x

PMID:15691311

Abstract

BACKGROUND

Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population.

MATERIAL AND METHODS

In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies.

RESULTS

Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the ()0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1()0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94).

CONCLUSION

Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.

摘要

背景

不同的人类白细胞抗原（HLA）-DQ基因与胃癌风险的增加或降低相关，但其与幽门螺杆菌感染状态的关联存在争议。在本研究中，我们评估了宿主HLA DQA1和DQB1基因座、幽门螺杆菌基因型以及社会经济因素对预测南欧人群中幽门螺杆菌相关远端胃癌的影响。

材料与方法

在一项前瞻性病例对照（1:2）研究中，42例幽门螺杆菌相关远端胃癌患者按年龄（±5岁）和性别与84例幽门螺杆菌相关良性胃十二指肠疾病患者（对照组）进行匹配。纳入时记录所接受的教育程度、吸烟状况、饮酒情况、胃癌的起源和家族史。通过内镜下胃黏膜活检确定HLA DQA1和DQB1分型以及幽门螺杆菌基因分型。

结果

与对照患者相比，远端胃癌患者中发现与cagA（+）菌株呈正相关（p <.002），与vacA-s2菌株呈负相关（p <.02）。在DQB1基因座，远端胃癌中（）0602等位基因比对照组更常见（26.2%对4.8%；p <.005）。在进行多重比较校正（精确多元回归分析）后，cagA（+）状态和DQB1（）0602等位基因与远端胃癌风险增加相关（分别为OR 3.7；95%CI = 1.33 - 12.26和OR 4.82；95%CI = 1.24 - 19.83），而vacA-s2状态与风险降低相关（OR 0.33；95%CI = 0.10 - 0.94）。