Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.

Non-clustered protocadherins (PCDHs) family is a group of cell-cell adhesion molecules. We have found differentially methylated genes in the non-clustered PCDHs family associated with Helicobacter pylori (H. pylori) infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of non-clustered PCDHs encoding genes in H. pylori-related gastric carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17 and PCDH20 were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in H. pylori positive subjects than the negative group (all P<0.001). Elevated methylation levels of PCDH10 and PCDH17 were observed with the increasing severity of gastric lesions (both Ptrend<0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR (95% CI) was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis (SG). In addition, PCDH10 expression was significantly lower in CAG (OR=0.40, 95% CI=0.24-0.68). The inverse association between methylation and protein expression of PCDH10 and PCDH17 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all P<0.001). Our study found elevated promoter methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early event in gastric carcinogenesis.

Objective To investigate the association between polymorphisms of the interleukin 10 ( IL10) gene and risk of gastric cancer (GC) and atrophic gastritis (AG). Methods This study enrolled patients with GC, patients with AG and healthy control subjects. Demographic data were collected and the IL10 gene -1082A/G, -819C/T and -592A/C polymorphisms were genotyped. An enzyme-linked immunosorbent assay was performed to detect Helicobacter pylori infection. Results The study enrolled 556 participants including 208 in the GC group, 116 in the AG group and 232 controls (CON group). In a recessive model of the IL10-819C/T polymorphism, a significantly decreased risk of GC was found compared with AG and non-cancer subjects, respectively (AG→GC: odds ratio OR 0.41; non-cancer→GC: OR 0.57). The CC genotype demonstrated a significantly increased risk of AG compared with CON. Similar significant results were detected in males and H. pylori-negative subgroups. The ACC haplotype was associated with a decreased risk of GC compared with AG. The ATC haplotype was associated with a decreased risk of AG compared with the CON group, but it was associated with an increased risk of GC compared with AG. Conclusion The IL10 gene promoter -819C/T (rs1800871) polymorphism was associated with the risk of GC and AG in a Chinese population.

This study assessed the effects of atrophic gastritis on bone mineral density (BMD) in premenopausal women in their 40s. We performed a retrospective analysis of medical records of premenopausal women in their 40s who underwent a health checkup, esophagogastroduodenoscopy, and bone densitometry at least thrice, 24 months apart, between January 2006 and December 2016. Based on first-visit esophagogastroduodenoscopy results, patients were divided into atrophic and non-atrophic gastritis groups; BMD changes over time were analyzed. Patients were further divided into subgroups depending on atrophic gastritis persistence; differences and absolute changes in BMD were assessed. BMD in both groups exhibited group-by-time interaction (p < 0.001). After adjusting for confounding factors, the mean BMD was significantly different at the 24-month and the 48-month follow-up (p = 0.049, p < 0.001, respectively). Subgroup analysis after adjusting for confounding factors showed a mean BMD of 1.128 and 1.104 at baseline, 1.110 and 1.100 at the 24-month follow-up, and 1.106 and 1.065 at the 48-month follow-up for persistent atrophic and non-atrophic gastritis groups, respectively. The difference between mean BMD was not significant at baseline (p = 0.171), but was significant at the 24-month and 48-month follow-ups (p = 0.044 and p < 0.001, respectively). Absolute changes in BMD over 48 months were - 0.010 and - 0.051 for the two subgroups, which was significantly different (p < 0.001). Atrophic gastritis reduces BMD in premenopausal women in their 40s. Patients with atrophic gastritis exhibited lower BMD than patients without, and patients with persistent atrophic gastritis exhibited a greater decrease in BMD.

The transition from chronic non-atrophic gastritis (CNAG) to chronic atrophic gastritis (CAG) and gastric carcinoma (GC) is regarded as a representative disease model of gastric mucosa malignant transformation led by uncontrolled inflammation. Traditional Chinese medicine (TCM) syndrome-targeted therapies have been applied in treating chronic gastritis (CG) malignant transformation in China with satisfying efficacy. This study aims to validate TCM syndrome features in each stage of CG malignant transformation. The findings may shed light on the TCM hypothesis of CG malignant transformation, and thus optimise syndrome-targeted treatment strategies of CNAG, CAG and GC, respectively.