Epigenetic alterations in Helicobacter pylori infection leading to gastric carcinogenesis: A systematic review

Abstract

Background: Gastric cancer (GC) is one of the top causes of cancer death worldwide, with 98% caused by Helicobacter pylori. The diverse disease presentation, asymptomatic H. pylori infection, and ineffective therapies lead to late diagnosis and high mortality. Chronic inflammation caused by H. pylori causes genetic and epigenetic modifications. Hence, this systematic review will address H. pylori‑related DNA methylation, histone modifications, and RNA alteration in GC. Materials and Methods: A comprehensive search of PubMed and Scopus was performed for publications from 2017 to August 2022. Studies involving GC regardless of type and location, H. pylori infection regardless of virulence factors, and epigenetic changes (DNA methylation, histone modification, and RNA alteration) were included. Studies of epigenetic changes in GC unrelated to H. pylori were excluded. All types of studies were taken into the analysis. Results: A final analysis includes 26 manuscripts, comprising 10 reviews and 16 original articles. Methylation levels in various gene promoters having a role in host defense, cell integrity and cell cycle, DNA repair, and apoptosis were altered in H. pylori infection preceding GC. In addition, H. pylori regulate specific genes through histone modifications. Different MicroRNA expressions were found in H. pylori GC patients, some acting as a tumor suppressor and influencing drug resistance. H. pylori eradication, to a certain extent of disease, can revert these epigenetic changes. Conclusion: Understanding the exact mechanism leading to carcinogenesis is required for GC early diagnosis and precise therapy to alleviate the disease burden.