Helicobacter pylori cagA and vacA Genotypes as Predictors of Progression of Gastric Preneoplastic Lesions: A Long-Term Follow-Up in a High-Risk Area in Spain

Helicobacter pylori cagA and vacA Genotypes as Predictors of Progression of Gastric Preneoplastic Lesions: A Long-Term Follow-Up in a High-Risk Area in Spain
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DOI:
10.1038/ajg.2011.1
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发表时间:
2011-05-01
影响因子:
9.8
通讯作者:
Sanz-Anquela, J. M.
Sanz-Anquela, J. M.
中科院分区:
医学1区
文献类型:
--
作者:
Gonzalez, Carlos A.;Figueiredo, Ceu;Sanz-Anquela, J. M.

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结论:目前还没有确定的胃癌前病变进展的预测标志物。本研究的目的是分析幽门螺杆菌cagA和vacA基因型和胃癌前病变的进展之间的关系。方法:这是一项后续研究,在西班牙的一个省进行胃癌的高风险。本研究共纳入了312例患者,这些患者在1988-1994年接受了胃镜检查和胃活检,诊断为正常粘膜、非萎缩性胃炎(NAG)、非化生性多灶性萎缩性胃炎(MAG)和完全或不完全肠化生(IM),并在2005-2007年接受了新的活检或在随访期间有终点。H. pylori cagA和vacA基因型直接在基线石蜡包埋的胃活检标本中进行PCR,然后反向杂交到线性探针测定。评估了观察者间和观察者内组织学诊断的变异性。结果:患者平均年龄为48.5岁(45%为男性),平均随访时间为12.8年。H. pylori菌株携带cagA、vacA s1和vacA m1基因型在更晚期胃癌前病变患者中更常见。cagA阳性、vacA s1和vacA m1菌株感染与胃癌前病变进展相关(分别为多变量比值比(OR)= 2.28,95%置信区间(CI)1.13-4.58; OR = 2.90,95% CI 1.38-6.13; OR = 3.38,95% CI 1.34-8.53)。同时cagA和vacA s1/m1阳性的菌株感染与胃癌前病变的进展相关,与cagA阴性/vacA s2/m2菌株感染相关的OR为4.80(95%CI 1.71-13.5)。pylori基因分型可能有助于鉴别胃癌前病变进展的高危患者和需要更密切监测的患者。
OBJECTIVES: There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions.METHODS: This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter-and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression.RESULTS: The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR) = 2.28, 95 % confidence interval (CI) 1.13-4.58; OR = 2.90, 95 % CI 1.38-6.13; and OR = 3.38, 95 % CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95 % CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains.CONCLUSIONS: H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.