Association of HLA gene polymorphisms with Helicobacter pylori related gastric cancer—a systematic review

Abstract

The appropriate host cell immune responses for the progression of several diseases, including gastric or stomach cancer (GC), are significantly influenced by HLA polymorphisms. Our objective was to systematically review the evidence linking HLA polymorphisms with the risk of Helicobacter. pylori related GC. We conducted a comprehensive literature search to identify studies published between 2000 and April 2023 on the association of HLA polymorphisms with H. pylori related GC using databases such as Medline through PubMed, Embase, Web of Science (core collection), The Cochrane Library, and Scopus. Two authors independently screened articles, extracted data, and assessed the risk of bias using the Risk of Bias Assessment tool for Non‐randomized Studies. From 7872 retrieved studies, 19 met inclusion criteria, encompassing 1656 cases and 16,787 controls across four World Health Organization regions, with Japan contributing the most studies. We explored HLA‐A/B/C, HLA‐DRB1/DQA1/DQB1, HLA‐G, and MICA alleles. Of 29 significant HLA polymorphisms identified, 18 showed a positive association with GC, whereas 11 were negatively associated. HLA‐DQB1*06 allele was most frequently associated to susceptibility, as reported in four studies, followed by HLA‐DRB1*04 and HLA‐DQA1*01, each reported in two studies. Conversely, HLA‐G*01, HLA‐DQA1*01, HLA‐DQA1*05, and HLA‐DQB1*03 were identified as protective in two studies each. Additionally, five genotypes and six haplotypes were reported as positive, whereas three genotypes and two haplotypes were negative factors for the disease incidence or mortality. Despite heterogeneity in the study population and types of HLA polymorphisms examined, our analysis indicates certain polymorphisms are associated with H. pylori related GC progression and mortality in specific populations.

Helicobacter pylori Infection in Patients with Gastric Cancer: A 2024 Update

“…[35] The development of GC and mortality related to H. pylori are linked to particular polymorphisms. [36] The TT genotype of rs7827435 and the CC genotype of rs10955176 may operate as protective factors against the risk of noncardia GC and H. pylori infection, respectively. [37] The course of an infection is determined by the interplay among virulence factors, phase-variable genes, and host genetics.…”

“…HLA polymorphisms have a major impact on proper host cell immunological responses for the development of several diseases, including GC. In certain groups at risk, the analysis revealed that some of the polymorphisms are linked to H. pylori -related GC development and cancer-related death, but no correlation was found between the variability of the study population and the types of HLA polymorphisms studied [ 36 ]. Single nucleotide polymorphisms (SNPs) in H. pylori infection and Mammalian sterile 20-like kinase 1 (MST1) along with MST2 were examined for their potential correlation with the incidence of noncardia GCs.…”