Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (IDIBELL-ICO), Barcelona, Spain.
Am J Gastroenterol. 2011 May;106(5):867-74. doi: 10.1038/ajg.2011.1. Epub 2011 Feb 1.
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.
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.
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.
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.
目前尚缺乏胃前病变进展的预测标志物。本研究旨在分析幽门螺杆菌 cagA 和 vacA 基因型与胃前病变进展之间的关系。
这是一项随访研究，在西班牙一个胃癌高发地区进行。共有 312 例患者于 1988-1994 年接受上消化道内镜检查和胃活检，诊断为正常黏膜、非萎缩性胃炎（NAG）、非多灶性萎缩性胃炎（MAG）、完全或不完全肠化生（IM），并在 2005-2007 年同意接受新的活检或在随访期间出现终点事件。直接在基线石蜡包埋胃活检标本中通过 PCR 后反向杂交到线探针检测来检测和表征 H. pylori cagA 和 vacA 基因型。评估组织学诊断的观察者间和观察者内变异性。使用无条件逻辑回归进行分析。
患者的平均年龄为 48.5 岁（45%为男性），平均随访时间为 12.8 年。携带 cagA、vacA s1 和 vacA m1 基因型的 H. pylori 菌株在胃前病变更严重的患者中更为常见。感染 cagA 阳性、vacA s1 和 vacA m1 菌株与胃前病变进展相关（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）。同时感染 cagA 阳性和 vacA s1/m1 的菌株与胃前癌前病变的进展相关，与感染 cagA 阴性/vacA s2/m2 菌株的 OR 为 4.80（95%CI 1.71-13.5）。
H. pylori 基因分型可用于识别胃前病变进展风险较高且需要更密切监测的患者。
