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哥斯达黎加血清胃蛋白酶原水平、幽门螺杆菌CagA状态及与胃前驱病变相关的细胞因子基因多态性

Serum pepsinogen levels, Helicobacter pylori CagA Status, and cytokine gene polymorphisms associated with gastric premalignant lesions in Costa Rica.

作者信息

Con Sergio A, Con-Wong Reinaldo, Con-Chin Gil R, Con-Chin Vicky G, Takeuchi Hiroaki, Valerín Ana L, Echandi Guillermo, Mena Fernando, Brenes Fernando, Yasuda Nobufumi, Araki Keijiro, Sugiura Tetsuro

机构信息

Centro Digestivo Doctores Con-Mediplaza, Pavas, San José, Costa Rica.

出版信息

Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2631-6. doi: 10.1158/1055-9965.EPI-07-0215.

DOI:10.1158/1055-9965.EPI-07-0215
PMID:18086767
Abstract

The detection of gastric premalignant lesions, atrophic gastritis, corpus atrophic gastritis, and intestinal metaplasia, using several potential markers was examined in Costa Rica. Depending on the lesion investigated, from a total of 223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG) and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human genomic DNAs were used for the genotyping of interleukin (IL)-1beta (-511 and +3954), IL-10 (-1082 and -592), and IL-1RN intron 2 by PCR and RFLP. Multivariate analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG levels (L-PG; PG I < or = 70 microg/L + PG I/II < or = 3), very low PG levels (VL-PG; PG I < or = 30 microg/L + PG I/II < or = 2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1beta +3954T-carrier and IL-1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for corpus atrophic gastritis detection, was the single marker with the highest combination of test characteristics, sensitivity (77.4%), specificity (80.7%), positive predictive value (39.3%), negative predictive value (95.7%), and seropositivity rate (27.4%), expected to improve after periodic measurements. Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and positive predictive value (62.2%), with similar sensitivity (74.2%) and negative predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with periodic measurements of serum PG, alone or in combination with CagA-ab status, to identify high gastric cancer risk, seems to be the method best suited for mass screening in Costa Rica.

摘要

在哥斯达黎加,研究了使用几种潜在标志物检测胃癌前病变、萎缩性胃炎、胃体萎缩性胃炎和肠化生的情况。根据所研究的病变,在总共223名消化不良患者中,分别有58例(26.0%)、31例(13.9%)或23例(10.3%)经组织学诊断为萎缩性胃炎、胃体萎缩性胃炎或肠化生。血清用于通过酶联免疫吸附测定(ELISA)测量胃蛋白酶原(PG)和幽门螺杆菌CagA抗体(CagA-ab)水平,人基因组DNA用于通过聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)对白细胞介素(IL)-1β(-511和+3954)、IL-10(-1082和-592)以及IL-1RN内含子2进行基因分型。进行多变量分析时对性别、年龄和幽门螺杆菌血清阳性进行了校正。低PG水平(L-PG;PG I≤70μg/L + PG I/II≤3)、极低PG水平(VL-PG;PG I≤30μg/L + PG I/II≤2)和CagA-ab分别与所有癌前病变相关,而IL-1β +3954T携带者和IL-1RN纯合2等位基因与肠化生相关。对于胃体萎缩性胃炎检测,VL-PG是具有最高检测特征组合的单一标志物,敏感性为77.4%,特异性为80.7%,阳性预测值为39.3%,阴性预测值为95.7%,血清阳性率为27.4%,定期测量后有望提高。VL-PG和CagA-ab联合检测提高了特异性(92.7%)和阳性预测值(62.2%),敏感性(74.2%)和阴性预测值(95.7%)相似。总之,通过定期测量血清PG单独或联合CagA-ab状态来检测胃体萎缩性胃炎以识别高胃癌风险,似乎是最适合哥斯达黎加大规模筛查的方法。

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