Kuipers E J, Pérez-Pérez G I, Meuwissen S G, Blaser M J
Department of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands.
J Natl Cancer Inst. 1995 Dec 6;87(23):1777-80. doi: 10.1093/jnci/87.23.1777.
Infection with Helicobacter pylori is a major risk factor for the development of atrophic gastritis and gastric cancer. H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen. H. pylori strains possessing cagA have been associated with enhanced induction of acute gastric inflammation.
We investigated the relationship between cagA status and the development of atrophic gastritis in a cohort of subjects infected with H. pylori.
Gastrointestinal endoscopy with biopsy sampling was used to study the natural history of gastritis in 58 subjects infected with H. pylori. Biopsy specimens were obtained before and after a mean follow-up period of 11.5 years (range, 10-13 years). The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein. Two-sided Fisher's exact tests, McNemar's tests, Student's t tests, and Wilcoxon sum rank tests were used to analyze the data.
Twenty-four (41%) of the 58 evaluated subjects had serum antibodies against CagA (i.e., they were cagA positive), and 34 subjects were cagA negative. At the initial visit, moderate to severe atrophic gastritis was observed in eight (33%) of the cagA-positive subjects and in six (18%) of the cagA-negative subjects. At that time, positive cagA status and gastric atrophy were not significantly related (P = .22; Fisher's exact test; odds ratio [OR] 2.33; 95% confidence interval [CI] = 0.58-9.65). During follow-up, 16 (36%) of the 44 initially atrophy-negative subjects developed atrophic gastritis (eight [50%] of 16 cagA-positive subjects versus eight [29%] of 28 cagA-negative subjects; P = .20, Fisher's exact test; relative risk [RR] = 1.75; 95% CI = 0.82-3.76). In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0). One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer. Four (29%) of the 14 subjects initially diagnosed with atrophic gastritis showed regression of atrophy during follow-up (one cagA positive and three cagA negative). Therefore, at the end of follow-up, 15 (62%) of the 24 cagA-positive subjects had atrophic gastritis compared with 11 (32%) of the 34 cagA-negative subjects (P = .02; Fisher's exact test; OR = 3.48; 95% CI = 1.02-12.18).
Infection with cagA-positive H. pylori strains is associated with an increased risk for the eventual development of atrophic gastritis and intestinal metaplasia.
幽门螺杆菌感染是萎缩性胃炎和胃癌发生的主要危险因素。幽门螺杆菌菌株在细胞毒素相关基因A（cagA）的存在方面可能存在差异，该基因编码一种高分子量免疫显性抗原。携带cagA的幽门螺杆菌菌株与急性胃炎症的诱导增强有关。
我们在一组感染幽门螺杆菌的受试者中研究了cagA状态与萎缩性胃炎发生之间的关系。
采用胃肠内镜活检采样来研究58例感染幽门螺杆菌受试者的胃炎自然病史。在平均11.5年（范围10 - 13年）的随访期前后获取活检标本。在随访时使用酶联免疫吸附试验确定每个个体的cagA状态，该试验旨在检测针对CagA蛋白的血清免疫球蛋白G的存在。使用双侧Fisher精确检验、McNemar检验、Student t检验和Wilcoxon秩和检验来分析数据。
58例评估受试者中有24例（41%）血清中有抗CagA抗体（即cagA阳性），34例受试者cagA阴性。在初次就诊时，cagA阳性受试者中有8例（33%）观察到中度至重度萎缩性胃炎，cagA阴性受试者中有6例（18%）。此时，cagA阳性状态与胃萎缩无显著相关性（P = 0.22；Fisher精确检验；比值比[OR] 2.33；95%置信区间[CI] = 0.58 - 9.65）。在随访期间，44例最初无萎缩的受试者中有16例（36%）发生了萎缩性胃炎（16例cagA阳性受试者中的8例[50%]与28例cagA阴性受试者中的8例[29%]；P = 0.20，Fisher精确检验；相对风险[RR] = 1.75；95% CI = 0.82 - 3.76）。在这16例受试者中的6例（5例cagA阳性与1例cagA阴性），萎缩性胃炎伴有肠化生的发生（即存在的特殊细胞类型发生改变）（P = 0.02；Fisher精确检验；RR = 9.06；95% CI = 1.16 - 71.0）。最初无萎缩的cagA阳性受试者中有1例发生了早期胃癌。14例最初诊断为萎缩性胃炎的受试者中有4例（29%）在随访期间萎缩有所消退（1例cagA阳性和3例cagA阴性）。因此，在随访结束时，24例cagA阳性受试者中有15例（62%）患有萎缩性胃炎，而34例cagA阴性受试者中有11例（32%）（P = 0.02；Fisher精确检验；OR = 3.48；95% CI = 1.02 - 12.18）。
感染cagA阳性幽门螺杆菌菌株与最终发生萎缩性胃炎和肠化生的风险增加有关。
