Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.

Gastric cancer (GC) ranks as the fifth most prevalent malignant neoplasm globally, with an increased death rate despite recent advancements in research and therapeutic options. Different molecular subtypes of GC have distinct interactions with the immune system, impacting the tumor microenvironment (TME), prognosis, and reaction to immunotherapy. Tumor-infiltrating lymphocytes (TILs) in the TME are crucial for preventing tumor growth and metastasis, as evidenced by research showing that patients with GC who have a significant density of TILs have better survival rates. But cancer cells have evolved a variety of mechanisms to evade immune surveillance, both sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) and Programmed Death-Ligand 1 (PD-L1) playing a pivotal role in the development of an immunosuppressive TME. They prevent T cell activation and proliferation resulting in a decrease in the immune system’s capacity to recognize and eliminate malignant cells. These immune checkpoint molecules function via different but complementary mechanisms, the expression of Siglec-15 being mutually exclusive with PD-L1 and, therefore, providing a different therapeutic approach. The review explores how TILs affect tumor growth and patient outcomes in GC, with particular emphasis on their interactions within the TME and potential targeting of the PD-L1 and Siglec-15 pathways for immunotherapy.

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p=0.01) as well as in premalignant lesions (p=0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20–4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19–3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72–4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37–0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Helicobacter (H.) pylori infection and duodenogastric reflux (DGR) are both linked to endoscopic and premalignant gastric lesion development, but it is still unclear whether they are independent or have a causal relationship. This study investigated the histologic gastric changes in patients with primary DGR and H. pylori infection, as well as their endoscopic findings, symptoms, drug consumption, and social behavior in comparison with patients presenting only DGR. The study included 560 patients with primary DGR on endoscopy divided into two groups, according to the presence/absence of H. pylori infection on biopsy (utilizing usual stainings and immunohistochemical methods). There was no significant difference in terms of age and sex, nor in the frequency of diabetes or esophagitis between the studied groups. Epigastric pain was associated with H. pylori‑positive biopsies in multivariate logistic regression analysis (P=0.005). Although without statistical significance, severe endoscopic lesions and premalignant gastric lesions were more frequent in the H. pylori group (45.1 vs. 28.4% and 37.4 vs. 32.3%, respectively). In patients with DGR, the final multivariate model revealed a positive association between smoking and immunohistochemically confirmed H. pylori infection (P=0.02, OR=1.88, 95% confidence intervals (CI)=1.10 to 3.21), but a negative effect of proton pump inhibitor consumption (P<0.001, OR=0.50, 95% CI=0.35 to 0.73). In conclusion, in patients with H. pylori infection and DGR, epigastric pain was the main reason for the endoscopic investigation. H. pylori infection over DGR did not influence the severity of endoscopic or premalignant gastric lesion development. Furthermore, smoking is directly related to immunohistochemically assessed active H. pylori infection in patients with bile reflux.

Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects.Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day).Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment.Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p=0.001), anticoagulants (p=0.029), nonsteroidal anti-inflammatory drugs (p=0.013), heart failure (p=0.007), liver (p=0.011) or cerebrovascular disease (p=0.004), diabetes mellitus (p=0.043), ulcer history (p=0.044), and alcohol consumption (p=0.018), but notHelicobacter pyloriinfection (p=0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06–8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09–30.58) or anticoagulants (OR 4.85, 95% CI 1.33–17.68), male gender (OR 5.2, 95% CI 1.77–15.34), and stroke (OR 7.27, 95% CI 1.40–37.74) remained predictors for ulcer on endoscopy.Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence ofH. pyloriinfection.