Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions
Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions
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DOI：
10.1093/jnci/djm120
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发表时间：
2007-09-05
期刊：
影响因子：
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通讯作者：
Kato, Ikuko
中科院分区：
文献类型：
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作者：
Plummer, Martyn;van Doorn, Leen-Jan;Kato, Ikuko
背景幽门螺杆菌感染与胃癌的发生有关。虽然感染H. pylori菌株中含有细胞毒素相关（cag A）基因（一种致病岛标记）可能增加萎缩性胃炎和胃癌的风险，致病性H. pylori基因的癌前病变的严重程度和进展是没有很好的defined.Methods胃活检标本，从2145名参与者在登记的化学预防试验在塔奇拉州，委内瑞拉，并进行组织学检查，以确定癌前病变的严重程度。H.用聚合酶链反应和特异性探针检测胃活检组织中的pylori DNA和根据cagA基因的存在或不存在的菌株类型。H. pylori DNA和组织学诊断用多分类Logistic回归分析。癌前病变的进展率和消退率由每年额外胃镜活检确定（平均随访= 3.5年）。所有统计学检验均为双侧检验。pylori感染与胃癌前病变的严重程度有关，而cagA阴性的H. pylori仅与慢性胃炎有关。以正常粘膜或浅表性胃炎患者为对照，cagA阳性患者与未感染者相比，异型增生的比值比为15.5（95%可信区间[CI] = 6.42 ~ 37.2），而cagA阴性H. pylori与未感染的人相比。cagA阳性H. pylori感染者比cagA阴性H. pylori感染之间的关系，但差异没有达到统计学意义。pylori DNA在胃活检和癌前病变的严重程度是特定的cagA阳性菌株。H.幽门螺杆菌和胃癌以前可能被低估，由于血清学H。pylori标志物和缺乏cagA基因型的区分。
Background Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H. pylori genes to the severity and progression of precancerous lesions is not well defined.Methods Gastric biopsy specimens were obtained at enrollment from 2145 participants in a chemoprevention trial in Tachira State, Venezuela, and examined histologically to determine the severity of precancerous lesions. The presence of H. pylori DNA in gastric biopsies and the strain type according to presence or absence of the cagA gene were detected by polymerase chain reaction and specific probes. The relationship between H. pylori DNA and histologic diagnosis was analyzed by polytomous logistic regression. Rates of progression and regression of precancerous lesions were determined from biopsies from additional annual gastroscopies (mean follow-up = 3.5 years). All statistical tests were two-sided.Results At enrollment, there was a strong association between cagA-positive H. pylori infection and the severity of gastric precancerous lesions, but cagA-negative H. pylori was associated only with chronic gastritis. Using individuals with normal mucosa or superficial gastritis as control subjects, the odds ratio for dysplasia was 15.5 (95% confidence interval [CI] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% CI = 0.37 to 2.17) for individuals infected with cagA-negative H. pylori compared with uninfected individuals. Individuals infected with cagA-positive H. pylori appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylori, but the differences did not attain statistical significance.Conclusions This large epidemiologic study shows a strong relationship between the presence of H. pylori DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylori and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylori markers and lack of discrimination by cagA genotype.