RESUMO
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 48.4â%; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7â%) showed progression of IM and six patients (1.9â%) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95â%CI 0.4-1.0). Family history (HR 1.5; 95â%CI 0.9-2.4) and smoking (HR 1.6; 95â%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.
RESUMO
BACKGROUND: Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena. AIMS: To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status. METHODS: This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects. RESULTS: In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. CONCLUSIONS: Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research.
