Association between HelicoBacter Pylori and Gastric Cancer

Association between HelicoBacter Pylori and Gastric Cancer

Helicobacter pylori is a gastric pathogen. Infection with H. pylori causes chronic inflammation and considerably raises the risk of gastric and duodenal ulcer disease and gastric cancer. Infection with H. pylori is a well known risk factor for the development of gastric cancer.
Gastric cancer is the second major cause of cancer-related deaths globally. Once H. pylori (colonizes about 50% of the world’s population) colonizes the gastric environment, it sticks with for the lifetime of the host. It suggests that the host immune response is unsuccessful in removing this bacterium.

In this blog we will discuss the association between helicobacter pylori and gastric cancer. To understand the link completely we will discuss:

  • What is Helicobacter pylori (H. pylori)?
  • How does H. pylori cause sickness?
  • What is gastric cancer?
  • How do H. pylori cause gastric cancer?
  • Conclusion

What is Helicobacter pylori (H. pylori)?

It is a type of bacteria, which can enter the body and live in the digestive tract. After several years, these germs can cause ulcers, in the lining of the stomach or the upper part of the small intestine. In some people infection with helicobacter can result in stomach cancer.
Infection with H. pylori is common and for the majority of people, it does not cause ulcers or other symptoms. If you face problems, then the medications can kill the germs and assist the healing of sores.

Now few people are getting the bacteria because more people get access to sanitation and clean water than before. Good health habits can help you to protect yourself from H. pylori.

How does H. pylori cause sickness?

H. pylori attacks the stomach lining when it enters the body. It generally protects from the acid, which the body uses for the digestion of food. After the sufficient damage by the bacteria, acid can penetrate through the lining that results in ulcers.
A person can get H. pylori from utensils, food or water or from the saliva or other body fluids of an infected person.

What is gastric cancer?

Gastric cancer is also called stomach. Infection with H. pylori is the famous cause of gastric cancer. Some of its other risk factors include chronic gastritis, old age, tobacco smoking, family history of stomach cancer and a history of stomach surgery for benign conditions.

Gastric cancer is divided into main classes:

  1. gastric cardia cancer- cancer of the top inch of the stomach, where it meet the esophagus
  2. non-cardia gastric cancer- cancer in all other areas of the stomach

How do H. pylori cause gastric cancer?

Epidemiologic studies revealed that the people infected with H. pylori have an increased risk of developing gastric cancer. The increased risk appears to be limited to non-cardia gastric cancer.

Following are the two broad mechanisms in which H. pylori infection may ultimately result in the development of gastric cancer:

Indirect effects through inflammatory processes:

H. pylori infection increases a chronic inflammatory response leading to an elevated cell turnover which after many decades, may lead to a buildup of mitotic errors. The step-by-step progression of inflammation of the corpus by H. pylori leads to atrophic gastritis, which is a risk factor for gastric cancer.

Atrophic gastritis results in increase in pH and achlorhydria. This alkaline atmosphere helps the colonization and propagation of H. pylori. On the other hand, with antral-predominant gastritis, hyperchlorhydria is seen leading to duodenal ulcer disorder which shows reduced risk for gastric cancer.

H. pylori infections at first cause antral gastritis, but continual infections cause hypochlorhydria, permitting the migration of bacteria leading to pangastritis and an elevated risk of adenocarcinoma. The clinical results depend on the relationship of the gastritis severity and distribution along with the acid secretion.

H. pylori-gastritis is primarily caused due to a CD4 Th1-cell response. Neutrophils and macrophages are taken that form an excess of  reactive nitrogen and reactive oxygen species, which along with the hydroxyl ion and the superoxide formed by H. pylori, lead to an elevated oxidative stress and DNA damage.

Continual infection of H. pylori involves a number of mechanisms. At first, H. pylori is able to defend itself from toxic substances like oxidative species. Secondly, H. pylori is able to encourage the apoptosis of macrophages.

Finally, it can augment the expression of proinflammatory factors. Cyclooxygenase-2 (COX-2) and gastric mucosal expression of multiple cytokines is augmented in the nucleus of the mucosal cells. This speeds up the development of atrophic changes and stimulates intracellular signaling transformation.

Abnormal DNA methylation in gastric epithelial cells takes place corresponding to the inflammatory response linked to H. pylori. It can include silencing effects on tumour suppressor genes.

Direct effects: H. pylori can show direct effects on the molecular make-up of the gastric epithelial cells. Mutations of cell-cycle controlling the genes, loss of adhesive properties of cells, deficiencies in DNA repair mechanisms and epigenetic variations can modify the behaviour of the cell leading to malignant transformation and cellular autonomy.

Two widely studied virulence causes are

  1. cytotoxin-associated gene A (CagA)
  2. vacuolating cytotoxin A (VacA)

These virulent strains are revealed to be linked with precancerous gastric lesions and development to a malignant phenotype. CagA positive strains have demonstrated to form a more strong inflammatory reaction leading to the succession from gastritis to atrophy and a high risk of gastric cancer.
CagA and peptidoglycan penetrate the epithelial cell through a bacterial type IV secretion system. CagA stimulates the multiple cellular signalling pathways. Peptidoglycan stimulates the phosphoinositide-3 kinase (PI3K-AKT) and NF-κB expression signalling pathways.

VacA adds to the durability of H. pylori infection by suppressing the T-cell response and disturbing the epithelial cell barrier. VacA strains are mainly cytotoxic and generate their effect by promoting the huge intracellular acid vacuoles in the gastric epithelial cells.
Furthermore, VacA can trouble the proliferation-apoptosis equilibrium by leading to the programmed cell death.

Conclusion

Persistent infection with H.pylori can lead to genomic instability inducing the gastric carcinogenesis progression.
However, H. pylori infection is not the only cause for the development of gastric cancer. Variations in lifestyle and dietary habits can help to decrease the occurrence of gastric cancer.

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