Nieuwenburg S A V, Mommersteeg M C, Eikenboom E L, Yu B, den Hollander W J, Holster I Lisanne, den Hoed Caroline M, Capelle L G, Tang Thjon J, Anten Marie-Paule, Prytz-Berset I, Witteman E M, Ter Borg F, Burger Jordy P W, Bruno Marco J, Fuhler G M, Peppelenbosch Maikel P, Doukas Michael, Kuipers Ernst J, Spaander Manon C W
Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Leiden University Medical Centre, Leiden, The Netherlands.
Endosc Int Open. 2021 Mar;9(3):E297-E305. doi: 10.1055/a-1314-6626. Epub 2021 Feb 18.
Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4-1.0). Family history (HR 1.5; 95 %CI 0.9-2.4) and smoking (HR 1.6; 95 %CI 0.9-2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of infection, and serological markers were not associated with progression. Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.
胃癌（GC）通常由胃黏膜上皮内瘤变（GPLs）如胃肠化生（GIM）发展而来。关于GIM肿瘤进展相关危险因素的信息较少。本研究旨在确定低GC发病率地区GIM进展的预测因素。胃癌前病变的进展与消退（PROREGAL）研究纳入了患有GPL的患者。患者接受了至少两次上消化道内镜检查及随机活检取样。GIM进展是指在随访（FU）期间根据OLGIM（胃肠化生手术链接）标准严重程度增加。通过问卷确定家族史和生活方式因素。检测血清感染情况、胃蛋白酶原（PG）、胃泌素-17和GC相关单核苷酸多态性（SNP）。进行Cox回归分析风险，进行卡方检验分析单核苷酸多态性。共纳入308例患者（纳入时中位年龄61岁，四分位间距（IQR）：17；男性占48.4%；中位随访时间48个月，IQR：24）。在随访期间，116例患者（37.7%）出现IM进展，6例患者（1.9%）发生高级别异型增生或GC。（rs11536889）上的次要等位基因（C）与GIM进展呈负相关（OR 0.6；95%CI 0.4 - 1.0）。家族史（HR 1.5；95%CI 0.9 - 2.4）和吸烟（HR 1.6；95%CI 0.9 - 2.7）显示出GIM进展的趋势。饮酒、体重指数、感染史和血清学标志物与进展无关。在低GC发病率国家，家族史和吸烟似乎与GIM进展风险增加有关。（rs11536889）显示出显著的负相关，表明遗传信息可能在GIM进展中起作用。
