Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study

S A V Nieuwenburg; M C Mommersteeg; E L Eikenboom; B Yu; W J den Hollander; I Lisanne Holster; Caroline M den Hoed; L G Capelle; Thjon J Tang; Marie-Paule Anten; I Prytz-Berset; E M Witteman; F Ter Borg; Jordy P W Burger; Marco J Bruno; G M Fuhler; Maikel P Peppelenbosch; Michael Doukas; Ernst J Kuipers; Manon C W Spaander

doi:10.1055/a-1314-6626

Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study

Endosc Int Open. 2021 Mar;9(3):E297-E305. doi: 10.1055/a-1314-6626. Epub 2021 Feb 18.

Authors

S A V Nieuwenburg¹, M C Mommersteeg¹, E L Eikenboom¹, B Yu¹, W J den Hollander², I Lisanne Holster¹, Caroline M den Hoed¹, L G Capelle³, Thjon J Tang⁴, Marie-Paule Anten⁵, I Prytz-Berset⁶, E M Witteman⁷, F Ter Borg⁸, Jordy P W Burger⁹, Marco J Bruno¹, G M Fuhler¹, Maikel P Peppelenbosch¹, Michael Doukas¹⁰, Ernst J Kuipers¹, Manon C W Spaander¹

Affiliations

¹ Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
² Leiden University Medical Centre, Leiden, The Netherlands.
³ Meander Medical Centre, Amersfoort, the Netherlands.
⁴ IJsselland Hospital, Capelle aan den IJssel, The Netherlands.
⁵ Sint Franciscus Hospital, Rotterdam, The Netherlands.
⁶ More and Romsdal Trust Ålesund, Ålesund, Norway.
⁷ Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
⁸ Deventer Hospital, Deventer, The Netherlands.
⁹ Department of Gastroenterology and Hepatology, Rijnstate, Arnhem, The Netherlands.
¹⁰ Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Abstract

Background and study aims 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. Patients and methods 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 Helicobacter pylori 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. Results 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 TLR4 (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 H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.

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