Role of Bacterial and Viral Pathogens in Gastric Carcinogenesis

Abstract

Gastric cancer (GC) is one of the deadliest malignancies worldwide. In contrast to many other tumor types, gastric carcinogenesis is tightly linked to infectious events. Infections with Helicobacter pylori (H. pylori) bacterium and Epstein–Barr virus (EBV) are the two most investigated risk factors for GC. These pathogens infect more than half of the world’s population. Fortunately, only a small fraction of infected individuals develops GC, suggesting high complexity of tumorigenic processes in the human stomach. Recent studies suggest that the multifaceted interplay between microbial, environmental, and host genetic factors underlies gastric tumorigenesis. Many aspects of these interactions still remain unclear. In this review, we update on recent discoveries, focusing on the roles of various gastric pathogens and gastric microbiome in tumorigenesis.

Helicobacter pylori pathogen inhibits cellular responses to oncogenic stress and apoptosis

“…Gastric carcinogenesis associated with H . pylori infection is determined by complex and still not well understood interactions between bacteria and human cells [ 2 ]. Previous studies have shown that one of the bacterial virulence determinants closely linked to tumorigenesis is CagA protein [ 3 ].…”

“…After translocation, CagA is phosphorylated by host tyrosine kinases at the EPIYA (Glu-Pro-Ile-Tyr-Ala) repeatable motifs located at the carboxy-terminal end of the CagA molecule. CagA is responsible for alteration of multiple signaling pathways and aberrant activation of various oncogenic proteins such as Ras, β-catenin, PI3K, and others [ 2 ]. The full spectrum of host interacting partners of CagA protein still remains unclear.…”

Helicobacter pylori and Epstein-Barr Virus Co-Infection in Polish Patients with Gastric Cancer – A Pilot Study

“…Neoplastic cells are characterized by reduced growth control, invasiveness to the tissues in which they occur, and the ability to spread. More and more often, attention is paid to the contribution to neoplasms formation by broadly understood infectious agents ( Fol and Jachowicz 2016 ; Masrour-Roudsari and Ebrahimpour 2017 ; Palrasu et al 2021 ). It is estimated that they could cause up to 20% of cancers.…”

“…Stomach cancer incidences and mortality vary greatly depending on environmental factors such as diet, alcohol consumption, smoking, cancer stage at diagnosis, and genetic burden. Helicobacter pylori and the Epstein-Barr virus are mentioned as significant risk factors for developing gastric cancer ( Fasciana et al 2019a ; Machlowska et al 2020 ; Sexton et al 2020 ; Palrasu et al 2021 ).…”

“…H. pylori was first isolated from the stomach in 1983, and already in 1994, the International Agency for Research on Cancer (IARC) classified H. pylori as a class 1 carcinogen ( Santacroce et al 2008 ; Fasciana et al 2019b ; Palrasu et al 2021 ). In most cases, the infection is asymptomatic, but 1–2% of people develop stomach cancer.…”